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词条 FHL2
释义

  1. Function

  2. Family

  3. Gene

  4. Tissue distribution

  5. Regulation of expression

  6. Clinical significance

      Breast cancer    Gastrointestinal cancer    Liver cancer    Prostate cancer  

  7. Interactions

  8. References

  9. Further reading

  10. External links

{{Infobox_gene}}Four and a half LIM domains protein 2 also known as FHL-2 is a protein that in humans is encoded by the FHL2 gene.[1] LIM proteins contain a highly conserved double zinc finger motif called the LIM domain.[2]

Function

FHL-2 is thought to have a role in the assembly of extracellular membranes and may function as a link between presenilin-2 and an intracellular signaling pathway.[2]

Family

The Four-and-a-half LIM (FHL)-only protein subfamily is one of the members of the LIM-only protein family. Protein members within the group might be originated from a common ancestor and share a high degree of similarity in their amino acid sequence.[3] These proteins are defined by the presence of the four and a half cysteine-rich LIM homeodomain with the half-domain always located in the N-terminal.[4] The name LIM was derived from the first letter of the transcription factors LIN-11, ISL-1 and MEC-3, from which the domain was originally characterized.[5] No direct interactions between LIM domain and DNA have been reported. Instead, extensive evidence points towards the functional role of FHL2 in supporting protein-protein interactions of LIM-containing proteins and its binding partners.[6][7][8][9] Thus far, five members have been categorized into the FHL subfamily, which are FHL1, FHL2, FHL3, FHL4 and activator of CREM in testis (ACT) in human.[10] FHL1, FHL2 and FHL3 are predominantly expressed in muscle,[11][13] while FHL4 and FHL5 are expressed exclusively in testis.[12]

Gene

FHL2 is the best studied member within the subfamily. The protein is encoded by the fhl2 gene being mapped in the region of human chromosome 2q12-q14.[13] Two alternative promoters, 1a and 1b, as well as 5 transcript variants of fhl2 have been reported.[14]

Tissue distribution

FHL2 exhibits diverse expression patterns in a cell/tissue-specific manner, which has been found in liver, kidney, lung, ovary, pancreas, prostate, stomach, colon, cortex, and in particular, the heart. However, its expression in some immune-related tissues like the spleen, thymus and blood leukocytes has not been documented.[15] Intriguingly, the FHL2 expression and function varies significantly between different types of cancer.[14][16][17][18] Such discrepancies are most likely due to the existence of the wide variety of transcription factors governing FHL2 expression.

Regulation of expression

Different transcription factors that have been reported responsible for the regulation of fhl2 expression include the well-known tumor suppressor protein p53,[14][19] serum response factor (SRF),[20][21] specificity protein 1 (Sp1).[22] the pleiotropic factor IL-1β,[23] MEF-2,[10] and activator protein-1 (AP-1).[24] Apart from being regulated by different transcription factors, FHL2 is itself involved extensively in regulating the expression of other genes. FHL2 exerts its transcriptional regulatory effects by functioning as an adaptor protein interacting indirectly with the targeted genes. In fact, LIM domain is a platform for the formation of multimeric protein complexes.[25] Therefore, FHL2 can contribute to human carcinogenesis by interacting with transcription factors of cancer-related genes and modulates the signaling pathways underlying the expression of these genes. Different types of cancer are associated with FHL2 which act either as the cancer suppressor or inducer, for example in breast cancer, gastrointestinal (GI) cancers, liver cancer and prostate cancer.

Clinical significance

The expression and functions of FHL2 varies greatly depending on the cancer types. It appeared that phenomenon is highly related to the differential mechanistic transcriptional regulations of FHL2 in the various types of cancer. However, the participation of fhl2 mutations and the posttranslational modifications of fhl2 in carcinogenesis cannot be ignored. In fact, functional mutation of fhl2 has been identified in a patient with familial dilated cardiomyopathy (DCM) and is associated with its pathogenesis.[26] This implied that fhl2 mutation may also profoundly affect the diverse cancer progressions. However, records describing the effects of fhl2 mutations on carcinogenesis are scarce.

Phosphorylation of FHL-2 protein has no significant effects on FHL2 functioning both in vitro and in vivo.[27][28] Provided that the existence of posttranscriptional modifications on FHL2 other than phosphorylation is still unclear and FHL2 functions almost exclusively through protein-protein interactions, research works in this direction is still interested. In particular, the mechanisms underpinning the subcellular localization of FHL2 should be focused. FHL2 can traffic freely between nuclear and the different cellular compartments.[10] It also interacts with other proteinaceous binding partners belonging to different functional classes including, but not limited to, transcription factors and signal transducers.[6][13][29][30] Therefore, FHL2 translocation could be important in regulating the different molecular signaling pathways which modify carcinogenesis, for example, nuclear translocation of FHL2 is related to aggressiveness and recurrence of prostate cancer[31] Similar evidence also has been identified in experiment using A7FIL+ cells and NIH 3T3 cell line as the disease model.[15][32][33]

Breast cancer

The FHL2 protein interacts with the breast cancer type 1 susceptibility gene (BRCA1) which enhances the transactivation of BRCA1.[34] In addition, intratumoral FHL2 level was one of the factors determining the worse survival of breast cancer patients[35]

Gastrointestinal cancer

FHL2 is related to gastrointestinal cancers and in particular, colon cancer. Fhl2 demonstrates an oncogenic property in colon cancer which induces the differentiation of some in vitro colon cancer models.[16][36][37] FHL2 is as well crucial to colon cancer cells invasion, migration and adhesion to extracellular matrix. The expression of FHL2 is positively regulated by transforming growth factor beta 1 (TGF-β1) stimulations which induces epithelial-mesenchymal transition (EMT) and endows cancer cells with metastatic properties. The TGF-β1-midiated alternation of FHL2 expression level might therefore trigger colon cell invasion. Besides, the subcellular localization of FHL2 can be modulated by TGF-β1 in sporadic colon cancer which resulted in the polymerization of alpha smooth muscle actin (α-SMA).[38] This process induces the fibroblast to take up a myofibroblast phenotype and contributes to cancer invasion. FHL2 can also induce EMT and cancer cell migration by affecting the structural integrity of membrane-associated E-cadherin-β-catenin complex.[39]

Liver cancer

In the most common form liver cancer, the hepatocellular carcinoma (HCC), FHL2 is always downregulated in the clinical samples.[14] Therefore, fhl2 is exhibiting a tumor-suppressive effect on HCC. Similar to p53, overexpression of FHL2 inhibit the proliferative activity of the HCC Hep3B cell line by decreasing its cyclin D1 expression and increasing P21 and P27 expression supporting the time-dependent cellular repair process.[40] Of note, a database of FHL2-regulated genes in murine liver has recently been established by using microarray and bioinformatics analysis, which provide useful information concerning most of the pathways and new genes related to FHL2.[41]

Prostate cancer

The molecular communication between androgen receptor (AR) and FHL2 is linked to the disease development of prostate cancer such as aggressiveness and biochemical recurrence (i.e., rise in circulatory prostate-specific antigen (PSA) levels after surgical or radiography treatment)[42][43] FHL2 expression is profoundly initiated by androgen through the mediation of serum response factor (SFR) and the RhoA / actin / megakaryocytic acute leukemia (MAL) signaling axis functioning upstream of SRF.[44][45] On the other hand, FHL2 is the coactivator of AR and is able to modulate AR signaling by altering the effect of Aryl hydrocarbon receptor (AhR) imposing AR activity with as yet unknown mechanisms.[46] Calpain cleavage of cytoskeletal protein filamin which is increased in prostate cancer could induce the nuclear translocation of FHL2, and this subsequently increase AR coactivation.[47]

Interactions

FHL2 has been shown to interact with:

{{div col|colwidth=20em}}
  • Androgen receptor,[48]
  • BRCA1,[49][50]
  • CTNNB1,[51]
  • CD18,[63]
  • CD29,[63]
  • CD49c,[63]
  • CREB1,[52]
  • EIF6,[63]
  • FHL3,[52][53]
  • IGFBP5,[54]
  • ITGA7,[55]
  • ITGB6,[56]
  • MAPK1,[57]
  • PSEN2,[58]
  • TRAF6,[59]
  • TTN,[60]
  • ZNF638,[61] and
  • ZBTB16.[62]
{{Div col end}}

References

1. ^{{cite journal | vauthors = Morgan MJ, Madgwick AJ | title = Slim defines a novel family of LIM-proteins expressed in skeletal muscle | journal = Biochem. Biophys. Res. Commun. | volume = 225 | issue = 2 | pages = 632–8 | date = October 1996 | pmid = 8753811 | pmc = | doi = 10.1006/bbrc.1996.1222 }}
2. ^1 {{cite web | title = Entrez Gene: FHL2 four and a half LIM domains 2| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2274| accessdate = }}
3. ^{{cite journal | vauthors = Fimia GM, De Cesare D, Sassone-Corsi P | title = A family of LIM-only transcriptional coactivators: tissue-specific expression and selective activation of CREB and CREM | journal = Molecular and Cellular Biology | volume = 20 | issue = 22 | date = Nov 2000 | pmid = 11046156 | doi=10.1128/mcb.20.22.8613-8622.2000 | pmc=102166 | pages=8613–8622}}
4. ^{{cite journal | vauthors = Kurakula K, Sommer D, Sokolovic M, Moerland PD, Scheij S, van Loenen PB, Koenis DS, Zelcer N, van Tiel CM, de Vries CJ | title = LIM-only protein FHL2 is a positive regulator of liver X receptors in smooth muscle cells involved in lipid homeostasis | journal = Molecular and Cellular Biology | volume = 35 | issue = 1 | date = Jan 2015 | pmid = 25332231 | doi = 10.1128/MCB.00525-14 | pages=52–62 | pmc=4295390}}
5. ^{{cite journal | vauthors = Way JC, Chalfie M | title = mec-3, a homeobox-containing gene that specifies differentiation of the touch receptor neurons in C. elegans | journal = Cell | volume = 54 | issue = 1 | date = Jul 1988 | pmid = 2898300 | pages=5–16 | doi=10.1016/0092-8674(88)90174-2}}
6. ^1 {{cite journal | vauthors = Schmeichel KL, Beckerle MC | title = The LIM domain is a modular protein-binding interface | journal = Cell | volume = 79 | issue = 2 | date = Oct 1994 | pmid = 7954790 | pages=211–9 | doi=10.1016/0092-8674(94)90191-0}}
7. ^{{cite journal | vauthors = Breen JJ, Agulnick AD, Westphal H, Dawid IB | title = Interactions between LIM domains and the LIM domain-binding protein Ldb1 | journal = The Journal of Biological Chemistry | volume = 273 | issue = 8 | date = Feb 1998 | pmid = 9468533 | pages=4712–7 | doi=10.1074/jbc.273.8.4712}}
8. ^{{cite journal | vauthors = Kadrmas JL, Beckerle MC | title = The LIM domain: from the cytoskeleton to the nucleus | journal = Nature Reviews Molecular Cell Biology | volume = 5 | issue = 11 | date = Nov 2004 | pmid = 15520811 | doi = 10.1038/nrm1499 | pages=920–31}}
9. ^{{cite journal | vauthors = Frank D, Kuhn C, Katus HA, Frey N | title = The sarcomeric Z-disc: a nodal point in signalling and disease | journal = Journal of Molecular Medicine | volume = 84 | issue = 6 | date = Jun 2006 | pmid = 16416311 | doi = 10.1007/s00109-005-0033-1 | pages=446–68}}
10. ^1 2 {{cite journal | vauthors = Johannessen M, Møller S, Hansen T, Moens U, Van Ghelue M | title = The multifunctional roles of the four-and-a-half-LIM only protein FHL2 | journal = Cellular and Molecular Life Sciences | volume = 63 | issue = 3 | date = Feb 2006 | pmid = 16389449 | doi = 10.1007/s00018-005-5438-z | pages=268–84}}
11. ^{{cite journal | vauthors = Samson T, Smyth N, Janetzky S, Wendler O, Müller JM, Schüle R, von der Mark H, von der Mark K, Wixler V | title = The LIM-only proteins FHL2 and FHL3 interact with alpha- and beta-subunits of the muscle alpha7beta1 integrin receptor | journal = The Journal of Biological Chemistry | volume = 279 | issue = 27 | date = Jul 2004 | pmid = 15117962 | doi = 10.1074/jbc.M312894200 | pages=28641–52}}
12. ^{{cite journal | vauthors = Morgan MJ, Madgwick AJ | title = The fourth member of the FHL family of LIM proteins is expressed exclusively in the testis | journal = Biochemical and Biophysical Research Communications | volume = 255 | issue = 2 | date = Feb 1999 | pmid = 10049694 | doi = 10.1006/bbrc.1999.0180 | pages=251–5}}
13. ^{{cite journal | vauthors = Chan KK, Tsui SK, Lee SM, Luk SC, Liew CC, Fung KP, Waye MM, Lee CY | title = Molecular cloning and characterization of FHL2, a novel LIM domain protein preferentially expressed in human heart | journal = Gene | volume = 210 | issue = 2 | date = Apr 1998 | pmid = 9573400 | doi=10.1016/S0378-1119(97)00644-6 | pages=345–50}}
14. ^1 2 3 {{cite journal | vauthors = Xu J, Zhou J, Li MS, Ng CF, Ng YK, Lai PB, Tsui SK | title = Transcriptional regulation of the tumor suppressor FHL2 by p53 in human kidney and liver cells | journal = PLOS ONE | volume = 9 | issue = 8 | pmid = 25121502 | doi = 10.1371/journal.pone.0099359 | year=2014 | pages=e99359 | pmc=4133229}}
15. ^1 {{cite journal | vauthors = Zheng Q, Zhao Y | title = The diverse biofunctions of LIM domain proteins: determined by subcellular localization and protein-protein interaction | journal = Biology of the Cell / Under the Auspices of the European Cell Biology Organization | volume = 99 | issue = 9 | date = Sep 2007 | pmid = 17696879 | doi = 10.1042/BC20060126 | pages=489–502}}
16. ^1 {{cite journal | vauthors = Wu Y, Guo Z, Zhang D, Zhang W, Yan Q, Shi X, Zhang M, Zhao Y, Zhang Y, Jiang B, Cheng T, Bai Y, Wang J | title = A novel colon cancer gene therapy using rAAV‑mediated expression of human shRNA-FHL2 | journal = International Journal of Oncology | volume = 43 | issue = 5 | date = Nov 2013 | pmid = 24008552 | doi = 10.3892/ijo.2013.2090 | pages=1618–26}}
17. ^{{cite journal | vauthors = Chan KK, Tsui SK, Ngai SM, Lee SM, Kotaka M, Waye MM, Lee CY, Fung KP | title = Protein-protein interaction of FHL2, a LIM domain protein preferentially expressed in human heart, with hCDC47 | journal = Journal of Cellular Biochemistry | volume = 76 | issue = 3 | date = Jan 2000 | pmid = 10649446 | doi=10.1002/(SICI)1097-4644(20000301)76:3<499::AID-JCB16>3.0.CO;2-4 | pages=499–508}}
18. ^{{cite journal | vauthors = Tanahashi H, Tabira T | title = Alzheimer's disease-associated presenilin 2 interacts with DRAL, an LIM-domain protein | journal = Human Molecular Genetics | volume = 9 | issue = 15 | date = Sep 2000 | pmid = 11001931 | doi=10.1093/oxfordjournals.hmg.a018919 | pages=2281–9}}
19. ^{{cite journal | vauthors = Tanahashi H, Tabira T | title = Alzheimer's disease-associated presenilin 2 interacts with DRAL, an LIM-domain protein | journal = Human Molecular Genetics | volume = 9 | issue = 15 | date = Sep 2000 | pmid = 11001931 | doi=10.1093/oxfordjournals.hmg.a018919 | pages=2281–9}}
20. ^{{cite journal | vauthors = Heemers HV, Regan KM, Dehm SM, Tindall DJ | title = Androgen induction of the androgen receptor coactivator four and a half LIM domain protein-2: evidence for a role for serum response factor in prostate cancer | journal = Cancer Research | volume = 67 | issue = 21 | date = Nov 2007 | pmid = 17975004 | doi = 10.1158/0008-5472.CAN-07-1917 | pages=10592–9}}
21. ^{{cite journal | vauthors = Philippar U, Schratt G, Dieterich C, Müller JM, Galgóczy P, Engel FB, Keating MT, Gertler F, Schüle R, Vingron M, Nordheim A | title = The SRF target gene Fhl2 antagonizes RhoA/MAL-dependent activation of SRF | journal = Molecular Cell | volume = 16 | issue = 6 | date = Dec 2004 | pmid = 15610731 | doi = 10.1016/j.molcel.2004.11.039 | pages=867–80}}
22. ^{{cite journal | vauthors = Guo Z, Zhang W, Xia G, Niu L, Zhang Y, Wang X, Zhang Y, Jiang B, Wang J | title = Sp1 upregulates the four and half lim 2 (FHL2) expression in gastrointestinal cancers through transcription regulation | journal = Molecular Carcinogenesis | volume = 49 | issue = 9 | date = Sep 2010 | pmid = 20607723 | doi = 10.1002/mc.20659 | pages=826–36}}
23. ^{{cite journal | vauthors = Joos H, Albrecht W, Laufer S, Reichel H, Brenner RE | title = IL-1beta regulates FHL2 and other cytoskeleton-related genes in human chondrocytes | journal = Molecular Medicine | volume = 14 | issue = 3–4 | pmid = 18224250 | doi = 10.2119/2007-00118.Joos | pages=150–9 | pmc=2213891}}
24. ^{{cite journal | vauthors = Morlon A, Sassone-Corsi P | title = The LIM-only protein FHL2 is a serum-inducible transcriptional coactivator of AP-1 | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 100 | issue = 7 | date = Apr 2003 | pmid = 12644711 | doi = 10.1073/pnas.0735923100 | pages=3977–82 | pmc=153033}}
25. ^{{cite journal | vauthors = Bach I | title = The LIM domain: regulation by association | journal = Mechanisms of Development | volume = 91 | issue = 1–2 | date = Mar 2000 | pmid = 10704826 | pages=5–17 | doi=10.1016/s0925-4773(99)00314-7}}
26. ^{{cite journal | vauthors = Arimura T, Hayashi T, Matsumoto Y, Shibata H, Hiroi S, Nakamura T, Inagaki N, Hinohara K, Takahashi M, Manatsu SI, Sasaoka T, Izumi T, Bonne G, Schwartz K, Kimura A | title = Structural analysis of four and half LIM protein-2 in dilated cardiomyopathy | journal = Biochemical and Biophysical Research Communications | volume = 357 | issue = 1 | date = May 2007 | pmid = 17416352 | doi = 10.1016/j.bbrc.2007.03.128 | pages=162–7}}
27. ^{{cite journal | vauthors = El Mourabit H, Müller S, Tunggal L, Paulsson M, Aumailley M | title = Characterization of recombinant and natural forms of the human LIM domain-containing protein FHL2 | journal = Protein Expression and Purification | volume = 32 | issue = 1 | date = Nov 2003 | pmid = 14680945 | doi = 10.1016/S1046-5928(03)00211-0 | pages=95–103}}
28. ^{{cite journal | vauthors = Purcell NH, Darwis D, Bueno OF, Müller JM, Schüle R, Molkentin JD | title = Extracellular signal-regulated kinase 2 interacts with and is negatively regulated by the LIM-only protein FHL2 in cardiomyocytes | journal = Molecular and Cellular Biology | volume = 24 | issue = 3 | date = Feb 2004 | pmid = 14729955 | doi=10.1128/mcb.24.3.1081-1095.2004 | pmc=321437 | pages=1081–1095}}
29. ^{{cite journal | vauthors = Wei Y, Renard CA, Labalette C, Wu Y, Lévy L, Neuveut C, Prieur X, Flajolet M, Prigent S, Buendia MA | title = Identification of the LIM protein FHL2 as a coactivator of beta-catenin | journal = The Journal of Biological Chemistry | volume = 278 | issue = 7 | date = Feb 2003 | pmid = 12466281 | doi = 10.1074/jbc.M207216200 | pages=5188–94}}
30. ^{{cite journal | vauthors = Lange S, Auerbach D, McLoughlin P, Perriard E, Schäfer BW, Perriard JC, Ehler E | title = Subcellular targeting of metabolic enzymes to titin in heart muscle may be mediated by DRAL/FHL-2 | journal = Journal of Cell Science | volume = 115 | issue = Pt 24 | date = Dec 2002 | pmid = 12432079 | doi=10.1242/jcs.00181 | pages=4925–36}}
31. ^{{cite journal | vauthors = Kahl P, Gullotti L, Heukamp LC, Wolf S, Friedrichs N, Vorreuther R, Solleder G, Bastian PJ, Ellinger J, Metzger E, Schüle R, Buettner R | title = Androgen receptor coactivators lysine-specific histone demethylase 1 and four and a half LIM domain protein 2 predict risk of prostate cancer recurrence | journal = Cancer Research | volume = 66 | issue = 23 | date = Dec 2006 | pmid = 17145880 | doi = 10.1158/0008-5472.CAN-06-1570 | pages=11341–7}}
32. ^{{cite journal | vauthors = Brown JR, Nigh E, Lee RJ, Ye H, Thompson MA, Saudou F, Pestell RG, Greenberg ME | title = Fos family members induce cell cycle entry by activating cyclin D1 | journal = Molecular and Cellular Biology | volume = 18 | issue = 9 | date = Sep 1998 | pmid = 9710644 | pages=5609–19 | doi=10.1128/mcb.18.9.5609 | pmc=109145}}
33. ^{{cite journal | vauthors = McGrath MJ, Binge LC, Sriratana A, Wang H, Robinson PA, Pook D, Fedele CG, Brown S, Dyson JM, Cottle DL, Cowling BS, Niranjan B, Risbridger GP, Mitchell CA | title = Regulation of the transcriptional coactivator FHL2 licenses activation of the androgen receptor in castrate-resistant prostate cancer | journal = Cancer Research | volume = 73 | issue = 16 | date = Aug 2013 | pmid = 23801747 | doi = 10.1158/0008-5472.CAN-12-4520 | pages=5066–79}}
34. ^{{cite journal | vauthors = Yan J, Zhu J, Zhong H, Lu Q, Huang C, Ye Q | title = BRCA1 interacts with FHL2 and enhances FHL2 transactivation function | journal = FEBS Letters | volume = 553 | issue = 1–2 | date = Oct 2003 | pmid = 14550570 | doi=10.1016/s0014-5793(03)00978-5 | pages=183–9}}
35. ^{{cite journal | vauthors = Gabriel B, Fischer DC, Orlowska-Volk M, zur Hausen A, Schüle R, Müller JM, Hasenburg A | title = Expression of the transcriptional coregulator FHL2 in human breast cancer: a clinicopathologic study | journal = Journal of the Society for Gynecologic Investigation | volume = 13 | issue = 1 | date = Jan 2006 | pmid = 16378916 | doi = 10.1016/j.jsgi.2005.10.001 | pages=69–75}}
36. ^{{cite journal | vauthors = Amann T, Egle Y, Bosserhoff AK, Hellerbrand C | title = FHL2 suppresses growth and differentiation of the colon cancer cell line HT-29 | journal = Oncology Reports | volume = 23 | issue = 6 | date = Jun 2010 | pmid = 20428824 | pages=1669–74 | doi = 10.3892/or_00000810 }}
37. ^{{cite journal | vauthors = Wang J, Yang Y, Xia HH, Gu Q, Lin MC, Jiang B, Peng Y, Li G, An X, Zhang Y, Zhuang Z, Zhang Z, Kung HF, Wong BC | title = Suppression of FHL2 expression induces cell differentiation and inhibits gastric and colon carcinogenesis | journal = Gastroenterology | volume = 132 | issue = 3 | date = Mar 2007 | pmid = 17383428 | doi = 10.1053/j.gastro.2006.12.004 | pages=1066–76}}
38. ^{{cite journal | vauthors = Gullotti L, Czerwitzki J, Kirfel J, Propping P, Rahner N, Steinke V, Kahl P, Engel C, Schüle R, Buettner R, Friedrichs N | title = FHL2 expression in peritumoural fibroblasts correlates with lymphatic metastasis in sporadic but not in HNPCC-associated colon cancer | journal = Laboratory Investigation | volume = 91 | issue = 12 | date = Dec 2011 | pmid = 21826055 | doi = 10.1038/labinvest.2011.109 | pages=1695–705}}
39. ^{{cite journal | vauthors = Zhang W, Jiang B, Guo Z, Sardet C, Zou B, Lam CS, Li J, He M, Lan HY, Pang R, Hung IF, Tan VP, Wang J, Wong BC | title = Four-and-a-half LIM protein 2 promotes invasive potential and epithelial-mesenchymal transition in colon cancer | journal = Carcinogenesis | volume = 31 | issue = 7 | date = Jul 2010 | pmid = 20460358 | doi = 10.1093/carcin/bgq094 | pages=1220–9}}
40. ^{{cite journal | vauthors = Ng CF, Ng PK, Lui VW, Li J, Chan JY, Fung KP, Ng YK, Lai PB, Tsui SK | title = FHL2 exhibits anti-proliferative and anti-apoptotic activities in liver cancer cells | journal = Cancer Letters | volume = 304 | issue = 2 | date = May 2011 | pmid = 21377781 | doi = 10.1016/j.canlet.2011.02.001 | pages=97–106}}
41. ^{{cite journal | vauthors = Ng CF, Xu JY, Li MS, Tsui SK | title = Identification of FHL2-regulated genes in liver by microarray and bioinformatics analysis | journal = Journal of Cellular Biochemistry | volume = 115 | issue = 4 | date = Apr 2014 | pmid = 24453047 | doi = 10.1002/jcb.24714 | pages=744–53}}
42. ^{{cite journal | vauthors = Heemers HV, Regan KM, Schmidt LJ, Anderson SK, Ballman KV, Tindall DJ | title = Androgen modulation of coregulator expression in prostate cancer cells | journal = Molecular Endocrinology | volume = 23 | issue = 4 | date = Apr 2009 | pmid = 19164447 | doi = 10.1210/me.2008-0363 | pages=572–83 | pmc=2667711}}
43. ^{{cite journal | vauthors = Uchio EM, Aslan M, Wells CK, Calderone J, Concato J | title = Impact of biochemical recurrence in prostate cancer among US veterans | journal = Archives of Internal Medicine | volume = 170 | issue = 15 | date = Aug 2010 | pmid = 20696967 | doi = 10.1001/archinternmed.2010.262 | pages=1390–5}}
44. ^{{cite journal | vauthors = Heemers HV, Regan KM, Schmidt LJ, Anderson SK, Ballman KV, Tindall DJ | title = Androgen modulation of coregulator expression in prostate cancer cells | journal = Molecular Endocrinology | volume = 23 | issue = 4 | date = Apr 2009 | pmid = 19164447 | doi = 10.1210/me.2008-0363 | pages=572–83 | pmc=2667711}}
45. ^{{cite journal | vauthors = Schmidt LJ, Duncan K, Yadav N, Regan KM, Verone AR, Lohse CM, Pop EA, Attwood K, Wilding G, Mohler JL, Sebo TJ, Tindall DJ, Heemers HV | title = RhoA as a mediator of clinically relevant androgen action in prostate cancer cells | journal = Molecular Endocrinology | volume = 26 | issue = 5 | date = May 2012 | pmid = 22456196 | doi = 10.1210/me.2011-1130 | pmc=3355556 | pages=716–35}}
46. ^{{cite journal | vauthors = Kollara A, Brown TJ | title = Four and a half LIM domain 2 alters the impact of aryl hydrocarbon receptor on androgen receptor transcriptional activity | journal = The Journal of Steroid Biochemistry and Molecular Biology | volume = 118 | issue = 1–2 | date = Jan 2010 | pmid = 19815066 | doi = 10.1016/j.jsbmb.2009.09.017 | pages=51–8}}
47. ^{{cite journal | vauthors = McGrath MJ, Binge LC, Sriratana A, Wang H, Robinson PA, Pook D, Fedele CG, Brown S, Dyson JM, Cottle DL, Cowling BS, Niranjan B, Risbridger GP, Mitchell CA | title = Regulation of the transcriptional coactivator FHL2 licenses activation of the androgen receptor in castrate-resistant prostate cancer | journal = Cancer Research | volume = 73 | issue = 16 | date = Aug 2013 | pmid = 23801747 | doi = 10.1158/0008-5472.CAN-12-4520 | pages=5066–79}}
48. ^{{cite journal | vauthors = Müller JM, Isele U, Metzger E, Rempel A, Moser M, Pscherer A, Breyer T, Holubarsch C, Buettner R, Schüle R | title = FHL2, a novel tissue-specific coactivator of the androgen receptor | journal = EMBO J. | volume = 19 | issue = 3 | pages = 359–69 | date = February 2000 | pmid = 10654935 | pmc = 305573 | doi = 10.1093/emboj/19.3.359 }}
49. ^{{cite journal | vauthors = Yan J, Zhu J, Zhong H, Lu Q, Huang C, Ye Q | title = BRCA1 interacts with FHL2 and enhances FHL2 transactivation function | journal = FEBS Lett. | volume = 553 | issue = 1–2 | pages = 183–9 | date = October 2003 | pmid = 14550570 | doi = 10.1016/s0014-5793(03)00978-5}}
50. ^{{cite journal | vauthors = Yan JH, Ye QN, Zhu JH, Zhong HJ, Zheng HY, Huang CF | title = [Isolation and characterization of a BRCA1-interacting protein] | journal = Yi Chuan Xue Bao | volume = 30 | issue = 12 | pages = 1161–6 | date = December 2003 | pmid = 14986435 | doi = }}
51. ^{{cite journal | vauthors = Wei Y, Renard CA, Labalette C, Wu Y, Lévy L, Neuveut C, Prieur X, Flajolet M, Prigent S, Buendia MA | title = Identification of the LIM protein FHL2 as a coactivator of beta-catenin | journal = J. Biol. Chem. | volume = 278 | issue = 7 | pages = 5188–94 | date = February 2003 | pmid = 12466281 | doi = 10.1074/jbc.M207216200 }}
52. ^1 {{cite journal | vauthors = Fimia GM, De Cesare D, Sassone-Corsi P | title = A family of LIM-only transcriptional coactivators: tissue-specific expression and selective activation of CREB and CREM | journal = Mol. Cell. Biol. | volume = 20 | issue = 22 | pages = 8613–22 | date = November 2000 | pmid = 11046156 | pmc = 102166 | doi = 10.1128/mcb.20.22.8613-8622.2000}}
53. ^{{cite journal | vauthors = Li HY, Ng EK, Lee SM, Kotaka M, Tsui SK, Lee CY, Fung KP, Waye MM | title = Protein-protein interaction of FHL3 with FHL2 and visualization of their interaction by green fluorescent proteins (GFP) two-fusion fluorescence resonance energy transfer (FRET) | journal = J. Cell. Biochem. | volume = 80 | issue = 3 | pages = 293–303 | year = 2001 | pmid = 11135358 | doi = 10.1002/1097-4644(20010301)80:3<293::AID-JCB10>3.0.CO;2-U}}
54. ^{{cite journal | vauthors = Amaar YG, Thompson GR, Linkhart TA, Chen ST, Baylink DJ, Mohan S | title = Insulin-like growth factor-binding protein 5 (IGFBP-5) interacts with a four and a half LIM protein 2 (FHL2) | journal = J. Biol. Chem. | volume = 277 | issue = 14 | pages = 12053–60 | date = April 2002 | pmid = 11821401 | doi = 10.1074/jbc.M110872200 }}
55. ^{{cite journal | vauthors = Samson T, Smyth N, Janetzky S, Wendler O, Müller JM, Schüle R, von der Mark H, von der Mark K, Wixler V | title = The LIM-only proteins FHL2 and FHL3 interact with alpha- and beta-subunits of the muscle alpha7beta1 integrin receptor | journal = J. Biol. Chem. | volume = 279 | issue = 27 | pages = 28641–52 | date = July 2004 | pmid = 15117962 | doi = 10.1074/jbc.M312894200 }}
56. ^1 2 3 4 {{cite journal | vauthors = Wixler V, Geerts D, Laplantine E, Westhoff D, Smyth N, Aumailley M, Sonnenberg A, Paulsson M | title = The LIM-only protein DRAL/FHL2 binds to the cytoplasmic domain of several alpha and beta integrin chains and is recruited to adhesion complexes | journal = J. Biol. Chem. | volume = 275 | issue = 43 | pages = 33669–78 | date = October 2000 | pmid = 10906324 | doi = 10.1074/jbc.M002519200 }}
57. ^{{cite journal | vauthors = Purcell NH, Darwis D, Bueno OF, Müller JM, Schüle R, Molkentin JD | title = Extracellular signal-regulated kinase 2 interacts with and is negatively regulated by the LIM-only protein FHL2 in cardiomyocytes | journal = Mol. Cell. Biol. | volume = 24 | issue = 3 | pages = 1081–95 | date = February 2004 | pmid = 14729955 | pmc = 321437 | doi = 10.1128/mcb.24.3.1081-1095.2004}}
58. ^{{cite journal | vauthors = Tanahashi H, Tabira T | title = Alzheimer's disease-associated presenilin 2 interacts with DRAL, an LIM-domain protein | journal = Hum. Mol. Genet. | volume = 9 | issue = 15 | pages = 2281–9 | date = September 2000 | pmid = 11001931 | doi = 10.1093/oxfordjournals.hmg.a018919}}
59. ^{{cite journal | vauthors = Bai S, Zha J, Zhao H, Ross FP, Teitelbaum SL | title = Tumor necrosis factor receptor-associated factor 6 is an intranuclear transcriptional coactivator in osteoclasts | journal = J. Biol. Chem. | volume = 283 | issue = 45 | pages = 30861–7 | date = November 2008 | pmid = 18768464 | pmc = 2662164 | doi = 10.1074/jbc.M802525200 }}
60. ^{{cite journal | vauthors = Lange S, Auerbach D, McLoughlin P, Perriard E, Schäfer BW, Perriard JC, Ehler E | title = Subcellular targeting of metabolic enzymes to titin in heart muscle may be mediated by DRAL/FHL-2 | journal = J. Cell Sci. | volume = 115 | issue = Pt 24 | pages = 4925–36 | date = December 2002 | pmid = 12432079 | doi = 10.1242/jcs.00181}}
61. ^1 2 {{cite journal | vauthors = Ng EK, Chan KK, Wong CH, Tsui SK, Ngai SM, Lee SM, Kotaka M, Lee CY, Waye MM, Fung KP | title = Interaction of the heart-specific LIM domain protein, FHL2, with DNA-binding nuclear protein, hNP220 | journal = J. Cell. Biochem. | volume = 84 | issue = 3 | pages = 556–66 | year = 2002 | pmid = 11813260 | doi = 10.1002/jcb.10041}}
62. ^{{cite journal | vauthors = McLoughlin P, Ehler E, Carlile G, Licht JD, Schäfer BW | title = The LIM-only protein DRAL/FHL2 interacts with and is a corepressor for the promyelocytic leukemia zinc finger protein | journal = J. Biol. Chem. | volume = 277 | issue = 40 | pages = 37045–53 | date = October 2002 | pmid = 12145280 | doi = 10.1074/jbc.M203336200 }}

Further reading

{{refbegin |33em}}
  • {{cite journal | vauthors = Genini M, Schwalbe P, Scholl FA, Remppis A, Mattei MG, Schäfer BW | title = Subtractive cloning and characterization of DRAL, a novel LIM-domain protein down-regulated in rhabdomyosarcoma | journal = DNA Cell Biol. | volume = 16 | issue = 4 | pages = 433–42 | year = 1997 | pmid = 9150430 | doi = 10.1089/dna.1997.16.433 }}
  • {{cite journal | vauthors = Chan KK, Tsui SK, Lee SM, Luk SC, Liew CC, Fung KP, Waye MM, Lee CY | title = Molecular cloning and characterization of FHL2, a novel LIM domain protein preferentially expressed in human heart | journal = Gene | volume = 210 | issue = 2 | pages = 345–50 | year = 1998 | pmid = 9573400 | doi = 10.1016/S0378-1119(97)00644-6 }}
  • {{cite journal | vauthors = Chan KK, Tsui SK, Ngai SM, Lee SM, Kotaka M, Waye MM, Lee CY, Fung KP | title = Protein-protein interaction of FHL2, a LIM domain protein preferentially expressed in human heart, with hCDC47 | journal = J. Cell. Biochem. | volume = 76 | issue = 3 | pages = 499–508 | year = 2000 | pmid = 10649446 | doi = 10.1002/(SICI)1097-4644(20000301)76:3<499::AID-JCB16>3.0.CO;2-4 }}
  • {{cite journal | vauthors = Müller JM, Isele U, Metzger E, Rempel A, Moser M, Pscherer A, Breyer T, Holubarsch C, Buettner R, Schüle R | title = FHL2, a novel tissue-specific coactivator of the androgen receptor | journal = EMBO J. | volume = 19 | issue = 3 | pages = 359–69 | year = 2000 | pmid = 10654935 | pmc = 305573 | doi = 10.1093/emboj/19.3.359 }}
  • {{cite journal | vauthors = Wixler V, Geerts D, Laplantine E, Westhoff D, Smyth N, Aumailley M, Sonnenberg A, Paulsson M | title = The LIM-only protein DRAL/FHL2 binds to the cytoplasmic domain of several alpha and beta integrin chains and is recruited to adhesion complexes | journal = J. Biol. Chem. | volume = 275 | issue = 43 | pages = 33669–78 | year = 2000 | pmid = 10906324 | doi = 10.1074/jbc.M002519200 }}
  • {{cite journal | vauthors = Tanahashi H, Tabira T | title = Alzheimer's disease-associated presenilin 2 interacts with DRAL, an LIM-domain protein | journal = Hum. Mol. Genet. | volume = 9 | issue = 15 | pages = 2281–9 | year = 2000 | pmid = 11001931 | doi = 10.1093/oxfordjournals.hmg.a018919 }}
  • {{cite journal | vauthors = Fimia GM, De Cesare D, Sassone-Corsi P | title = A family of LIM-only transcriptional coactivators: tissue-specific expression and selective activation of CREB and CREM | journal = Mol. Cell. Biol. | volume = 20 | issue = 22 | pages = 8613–22 | year = 2000 | pmid = 11046156 | pmc = 102166 | doi = 10.1128/MCB.20.22.8613-8622.2000 }}
  • {{cite journal | vauthors = Scholl FA, McLoughlin P, Ehler E, de Giovanni C, Schäfer BW | title = DRAL is a p53-responsive gene whose four and a half LIM domain protein product induces apoptosis | journal = J. Cell Biol. | volume = 151 | issue = 3 | pages = 495–506 | year = 2000 | pmid = 11062252 | pmc = 2185594 | doi = 10.1083/jcb.151.3.495 }}
  • {{cite journal | vauthors = Li HY, Kotaka M, Kostin S, Lee SM, Kok LD, Chan KK, Tsui SK, Schaper J, Zimmermann R, Lee CY, Fung KP, Waye MM | title = Translocation of a human focal adhesion LIM-only protein, FHL2, during myofibrillogenesis and identification of LIM2 as the principal determinants of FHL2 focal adhesion localization | journal = Cell Motil. Cytoskeleton | volume = 48 | issue = 1 | pages = 11–23 | year = 2001 | pmid = 11124707 | doi = 10.1002/1097-0169(200101)48:1<11::AID-CM2>3.0.CO;2-I }}
  • {{cite journal | vauthors = Li HY, Ng EK, Lee SM, Kotaka M, Tsui SK, Lee CY, Fung KP, Waye MM | title = Protein-protein interaction of FHL3 with FHL2 and visualization of their interaction by green fluorescent proteins (GFP) two-fusion fluorescence resonance energy transfer (FRET) | journal = J. Cell. Biochem. | volume = 80 | issue = 3 | pages = 293–303 | year = 2001 | pmid = 11135358 | doi = 10.1002/1097-4644(20010301)80:3<293::AID-JCB10>3.0.CO;2-U }}
  • {{cite journal | vauthors = Dye BT, Patton JG | title = An RNA recognition motif (RRM) is required for the localization of PTB-associated splicing factor (PSF) to subnuclear speckles | journal = Exp. Cell Res. | volume = 263 | issue = 1 | pages = 131–44 | year = 2001 | pmid = 11161712 | doi = 10.1006/excr.2000.5097 }}
  • {{cite journal | vauthors = Ng EK, Chan KK, Wong CH, Tsui SK, Ngai SM, Lee SM, Kotaka M, Lee CY, Waye MM, Fung KP | title = Interaction of the heart-specific LIM domain protein, FHL2, with DNA-binding nuclear protein, hNP220 | journal = J. Cell. Biochem. | volume = 84 | issue = 3 | pages = 556–66 | year = 2002 | pmid = 11813260 | doi = 10.1002/jcb.10041 }}
  • {{cite journal | vauthors = Amaar YG, Thompson GR, Linkhart TA, Chen ST, Baylink DJ, Mohan S | title = Insulin-like growth factor-binding protein 5 (IGFBP-5) interacts with a four and a half LIM protein 2 (FHL2) | journal = J. Biol. Chem. | volume = 277 | issue = 14 | pages = 12053–60 | year = 2002 | pmid = 11821401 | doi = 10.1074/jbc.M110872200 }}
  • {{cite journal | vauthors = Stilo R, Leonardi A, Formisano L, Di Jeso B, Vito P, Liguoro D | title = TUCAN/CARDINAL and DRAL participate in a common pathway for modulation of NF-kappaB activation | journal = FEBS Lett. | volume = 521 | issue = 1–3 | pages = 165–9 | year = 2002 | pmid = 12067710 | doi = 10.1016/S0014-5793(02)02869-7 }}
  • {{cite journal | vauthors = McLoughlin P, Ehler E, Carlile G, Licht JD, Schäfer BW | title = The LIM-only protein DRAL/FHL2 interacts with and is a corepressor for the promyelocytic leukemia zinc finger protein | journal = J. Biol. Chem. | volume = 277 | issue = 40 | pages = 37045–53 | year = 2002 | pmid = 12145280 | doi = 10.1074/jbc.M203336200 }}
  • {{cite journal | vauthors = Jiang LQ, Wen SJ, Wang HY, Chen LY | title = Screening the proteins that interact with calpain in a human heart cDNA library using a yeast two-hybrid system | journal = Hypertens. Res. | volume = 25 | issue = 4 | pages = 647–52 | year = 2002 | pmid = 12358155 | doi = 10.1291/hypres.25.647 }}
  • {{cite journal | vauthors = Schlisio S, Halperin T, Vidal M, Nevins JR | title = Interaction of YY1 with E2Fs, mediated by RYBP, provides a mechanism for specificity of E2F function | journal = EMBO J. | volume = 21 | issue = 21 | pages = 5775–86 | year = 2002 | pmid = 12411495 | pmc = 131074 | doi = 10.1093/emboj/cdf577 }}
  • {{cite journal | vauthors = Lange S, Auerbach D, McLoughlin P, Perriard E, Schäfer BW, Perriard JC, Ehler E | title = Subcellular targeting of metabolic enzymes to titin in heart muscle may be mediated by DRAL/FHL-2 | journal = J. Cell Sci. | volume = 115 | issue = Pt 24 | pages = 4925–36 | year = 2002 | pmid = 12432079 | doi = 10.1242/jcs.00181 }}
  • {{cite journal | vauthors = Wei Y, Renard CA, Labalette C, Wu Y, Lévy L, Neuveut C, Prieur X, Flajolet M, Prigent S, Buendia MA | title = Identification of the LIM protein FHL2 as a coactivator of beta-catenin | journal = J. Biol. Chem. | volume = 278 | issue = 7 | pages = 5188–94 | year = 2003 | pmid = 12466281 | doi = 10.1074/jbc.M207216200 }}
{{refend}}

External links

  • {{MeshName|FHL2+protein,+human}}
{{NLM content}}{{PDB Gallery|geneid=2274}}{{Transcription factors|g3}}

1 : Transcription factors
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