请输入您要查询的百科知识：

　

词条 DAP3
释义

  1. Structure

  2. Function

  3. Clinical significance

  4. Interactions

  5. References

  6. Further reading

{{Infobox_gene}}

28S ribosomal protein S29, mitochondrial, also known as death-associated protein 3 (DAP3), is a protein that in humans is encoded by the DAP3 gene on chromosome 1.[1][2][3][4] This gene encodes a 28S subunit protein of the mitochondrial ribosome (mitoribosome) and plays key roles in translation, cellular respiration, and apoptosis.[3][4][5][6] Moreover, DAP3 is associated with cancer development, but has been observed to aid some cancers while suppressing others.[6][7][8]

Structure

The DAP3 gene encodes a 46 kDa protein located in the lower area of the small mitoribosomal subunit.[5][8][9][10] This protein contains a P-loop motif that binds GTP and a highly conserved 17-residue targeting sequence responsible for its localization to the mitochondria.[5][7][8][9] Of interest, many of the phosphorylation sites on this protein are highly conserved and clustered around GTP-binding motifs.[5]

Several splice variants were observed in human ESTs that differ largely in the 5’ UTR region.[3][10] Pseudogenes for this gene are also found in chromosomes 1 and 2.[3]

Function

DAP3 is a 28S subunit protein of mitoribosomes and localizes to the mitochondrial matrix.[3][4][5] As part of the mitoribosome, DAP3 participates in the translation of the 13 ETC complex proteins encoded in the mitochondrial genome, and consequently, in the regulation of cellular respiration.[3][4][5][6] As a member of the death-associated protein (DAP) family, DAP3 can also be found outside of the mitochondria to initiate the extrinsic apoptotic pathway through its interactions with apoptotic factors, such as tumor necrosis factor-alpha, Fas ligand, and gamma interferon.[3][4][7][8][9] Additionally, DAP3 interacts with the factor IPS-1 to activate caspases 3, 8, and 9, resulting in a type of extracellular apoptosis called anoikis.[8][9] Moreover, DAP3 may contribute to apoptosis through its mediation of mitochondrial fragmentation, as this function extends to the mediation of the oxidative stress response, reactive oxygen species (ROS) production, and ultimately, mitochondrial homeostasis.[6][7][9] DAP3 is essential for life, and its deletion in embryos is lethal.[10] Nonetheless, DAP3 and its apoptotic activity can be inhibited by AKT phosphorylation.[8][9]

Clinical significance

As aforementioned, death associated protein 3 (DAP3) has regulatory roles in cell respiration and apoptosis. Both opposites and cell respiration are important elements of cell death pathways and have underlying mechanistic roles in ischemia-reperfusion injury.[11][12][13]

During a normal embryologic processes, or during cell injury (such as ischemia-reperfusion injury during heart attacks and strokes) or during developments and processes in cancer, an apoptotic cell undergoes structural changes including cell shrinkage, plasma membrane blebbing, nuclear condensation, and fragmentation of the DNA and nucleus. This is followed by fragmentation into apoptotic bodies that are quickly removed by phagocytes, thereby preventing an inflammatory response.[14] It is a mode of cell death defined by characteristic morphological, biochemical and molecular changes. It was first described as a "shrinkage necrosis", and then this term was replaced by apoptosis to emphasize its role opposite mitosis in tissue kinetics. In later stages of apoptosis the entire cell becomes fragmented, forming a number of plasma membrane-bounded apoptotic bodies which contain nuclear and or cytoplasmic elements. The ultrastructural appearance of necrosis is quite different, the main features being mitochondrial swelling, plasma membrane breakdown and cellular disintegration. Apoptosis occurs in many physiological and pathological processes. It plays an important role during embryonal development as programmed cell death and accompanies a variety of normal involutional processes in which it serves as a mechanism to remove "unwanted" cells.

DAP3 has been implicated in numerous cancers. Studies demonstrated that DAP3 expression tended to be low to nonexistent in the tumor cells of B-cell lymphoma, non-small cell lung cancer, head and neck cancer, breast cancer, gastric cancer, and colon cancer, possibly due to hypermethylation of the gene’s promoter.[7][8] Moreover, DAP3 expression has been positively correlated with improved cancer prognosis, indicating that the protein combats cancer progression through its proapoptotic function.[7][8] As a result, DAP3 could serve as a potential biomarker to monitor the effectiveness of therapeutic treatments such as chemotherapy.[7]

However, in other cancers, such as glioblastoma multiforme (GBM) and thymoma, DAP3 expression was found to be upregulated.[6][10] Thus, the specific role of DAP3 in various cancers requires further study.[13]

Interactions

DAP3 has been shown to interact with:

  • DELE,[8]
  • IPS-1,[8]
  • AKT,[8]
  • PKA,[10]
  • PKC,[10]
  • NOA1,[4][10]
  • FADD,[15]
  • Glucocorticoid receptor,[16]
  • Heat shock protein 90kDa alpha (cytosolic), member A1,[16] and
  • TNFRSF10A.[15]

References

1. ^{{cite journal | vauthors = Kissil JL, Deiss LP, Bayewitch M, Raveh T, Khaspekov G, Kimchi A | title = Isolation of DAP3, a novel mediator of interferon-gamma-induced cell death | journal = The Journal of Biological Chemistry | volume = 270 | issue = 46 | pages = 27932–6 | date = Nov 1995 | pmid = 7499268 | pmc = | doi = 10.1074/jbc.270.46.27932 }}
2. ^{{cite journal | vauthors = Kissil JL, Kimchi A | title = Assignment of death associated protein 3 (DAP3) to human chromosome 1q21 by in situ hybridization | journal = Cytogenetics and Cell Genetics | volume = 77 | issue = 3–4 | pages = 252 | date = September 1997 | pmid = 9284927 | pmc = | doi = 10.1159/000134587 }}
3. ^1 2 3 4 5 6 {{cite web | title = Entrez Gene: DAP3 death associated protein 3| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7818| accessdate = }}
4. ^1 2 3 4 5 {{cite journal | vauthors = Tang T, Zheng B, Chen SH, Murphy AN, Kudlicka K, Zhou H, Farquhar MG | title = hNOA1 interacts with complex I and DAP3 and regulates mitochondrial respiration and apoptosis | journal = The Journal of Biological Chemistry | volume = 284 | issue = 8 | pages = 5414–24 | date = Feb 2009 | pmid = 19103604 | doi = 10.1074/jbc.M807797200 | pmc=2643507}}
5. ^1 2 3 4 5 {{cite journal | vauthors = Miller JL, Koc H, Koc EC | title = Identification of phosphorylation sites in mammalian mitochondrial ribosomal protein DAP3 | journal = Protein Science | volume = 17 | issue = 2 | pages = 251–60 | date = Feb 2008 | pmid = 18227431 | doi = 10.1110/ps.073185608 | pmc=2222727}}
6. ^1 2 3 4 {{cite journal | vauthors = Jacques C, Fontaine JF, Franc B, Mirebeau-Prunier D, Triau S, Savagner F, Malthiery Y | title = Death-associated protein 3 is overexpressed in human thyroid oncocytic tumours | journal = British Journal of Cancer | volume = 101 | issue = 1 | pages = 132–8 | date = Jul 2009 | pmid = 19536094 | doi = 10.1038/sj.bjc.6605111 | pmc=2713694}}
7. ^1 2 3 4 5 6 {{cite journal | vauthors = Jia Y, Ye L, Ji K, Zhang L, Hargest R, Ji J, Jiang WG | title = Death-associated protein-3, DAP-3, correlates with preoperative chemotherapy effectiveness and prognosis of gastric cancer patients following perioperative chemotherapy and radical gastrectomy | journal = British Journal of Cancer | volume = 110 | issue = 2 | pages = 421–9 | date = Jan 2014 | pmid = 24300973 | doi = 10.1038/bjc.2013.712 | pmc=3899757}}
8. ^1 2 3 4 5 6 7 8 9 10 {{cite journal | vauthors = Wazir U, Jiang WG, Sharma AK, Mokbel K | title = The mRNA expression of DAP3 in human breast cancer: correlation with clinicopathological parameters | journal = Anticancer Research | volume = 32 | issue = 2 | pages = 671–4 | date = Feb 2012 | pmid = 22287761 }}
9. ^1 2 3 4 5 {{cite journal | vauthors = Miyazaki T, Shen M, Fujikura D, Tosa N, Kim HR, Kon S, Uede T, Reed JC | title = Functional role of death-associated protein 3 (DAP3) in anoikis | journal = The Journal of Biological Chemistry | volume = 279 | issue = 43 | pages = 44667–72 | date = Oct 2004 | pmid = 15302871 | doi = 10.1074/jbc.M408101200 }}
10. ^1 2 3 4 5 6 {{cite journal | vauthors = Han MJ, Chiu DT, Koc EC | title = Regulation of mitochondrial ribosomal protein S29 (MRPS29) expression by a 5'-upstream open reading frame | journal = Mitochondrion | volume = 10 | issue = 3 | pages = 274–83 | date = Apr 2010 | pmid = 20079882 | doi = 10.1016/j.mito.2009.12.150 | pmc=2844934}}
11. ^{{cite journal | vauthors = Gracia-Sancho J, Casillas-Ramírez A, Peralta C | title = Molecular pathways in protecting the liver from ischaemia/reperfusion injury: a 2015 update | journal = Clinical Science | volume = 129 | issue = 4 | pages = 345–62 | date = Aug 2015 | pmid = 26014222 | doi = 10.1042/CS20150223 }}
12. ^{{cite journal | vauthors = Ekert PG, Vaux DL | title = The mitochondrial death squad: hardened killers or innocent bystanders? | journal = Current Opinion in Cell Biology | volume = 17 | issue = 6 | pages = 626–30 | date = Dec 2005 | pmid = 16219456 | doi = 10.1016/j.ceb.2005.09.001 }}
13. ^1 {{cite journal | vauthors = Kissil JL, Kimchi A | title = Death-associated proteins: from gene identification to the analysis of their apoptotic and tumour suppressive functions | journal = Molecular Medicine Today | volume = 4 | issue = 6 | pages = 268–74 | date = Jun 1998 | pmid = 9679246 | doi=10.1016/s1357-4310(98)01263-5}}
14. ^{{cite journal | vauthors = Kerr JF, Wyllie AH, Currie AR | title = Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics | journal = British Journal of Cancer | volume = 26 | issue = 4 | pages = 239–57 | date = Aug 1972 | pmid = 4561027 | doi=10.1038/bjc.1972.33 | pmc=2008650}}
15. ^1 {{cite journal | vauthors = Miyazaki T, Reed JC | title = A GTP-binding adapter protein couples TRAIL receptors to apoptosis-inducing proteins | journal = Nature Immunology | volume = 2 | issue = 6 | pages = 493–500 | date = Jun 2001 | pmid = 11376335 | doi = 10.1038/88684 }}
16. ^1 {{cite journal | vauthors = Hulkko SM, Wakui H, Zilliacus J | title = The pro-apoptotic protein death-associated protein 3 (DAP3) interacts with the glucocorticoid receptor and affects the receptor function | journal = The Biochemical Journal | volume = 349 | issue = 3| pages = 885–93 | date = Aug 2000 | pmid = 10903152 | pmc = 1221218 | doi = 10.1042/bj3490885}}

Further reading

{{refbegin | 2}}
  • {{cite journal | vauthors = Maruyama K, Sugano S | title = Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides | journal = Gene | volume = 138 | issue = 1–2 | pages = 171–4 | year = 1994 | pmid = 8125298 | doi = 10.1016/0378-1119(94)90802-8 }}
  • {{cite journal | vauthors = Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S | title = Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library | journal = Gene | volume = 200 | issue = 1–2 | pages = 149–56 | year = 1997 | pmid = 9373149 | doi = 10.1016/S0378-1119(97)00411-3 }}
  • {{cite journal | vauthors = Hulkko SM, Wakui H, Zilliacus J | title = The pro-apoptotic protein death-associated protein 3 (DAP3) interacts with the glucocorticoid receptor and affects the receptor function | journal = Biochem. J. | volume = 349 | issue = Pt 3 | pages = 885–93 | year = 2000 | pmid = 10903152 | pmc = 1221218 | doi = 10.1042/bj3490885}}
  • {{cite journal | vauthors = Morgan CJ, Jacques C, Savagner F, Tourmen Y, Mirebeau DP, Malthièry Y, Reynier P | title = A conserved N-terminal sequence targets human DAP3 to mitochondria | journal = Biochem. Biophys. Res. Commun. | volume = 280 | issue = 1 | pages = 177–81 | year = 2001 | pmid = 11162496 | doi = 10.1006/bbrc.2000.4119 }}
  • {{cite journal | vauthors = Cavdar Koc E, Ranasinghe A, Burkhart W, Blackburn K, Koc H, Moseley A, Spremulli LL | title = A new face on apoptosis: death-associated protein 3 and PDCD9 are mitochondrial ribosomal proteins | journal = FEBS Lett. | volume = 492 | issue = 1–2 | pages = 166–70 | year = 2001 | pmid = 11248257 | doi = 10.1016/S0014-5793(01)02250-5 }}
  • {{cite journal | vauthors = Cavdar Koc E, Burkhart W, Blackburn K, Moseley A, Spremulli LL | title = The small subunit of the mammalian mitochondrial ribosome. Identification of the full complement of ribosomal proteins present | journal = J. Biol. Chem. | volume = 276 | issue = 22 | pages = 19363–74 | year = 2001 | pmid = 11279123 | doi = 10.1074/jbc.M100727200 }}
  • {{cite journal | vauthors = Miyazaki T, Reed JC | title = A GTP-binding adapter protein couples TRAIL receptors to apoptosis-inducing proteins | journal = Nat. Immunol. | volume = 2 | issue = 6 | pages = 493–500 | year = 2001 | pmid = 11376335 | doi = 10.1038/88684 }}
  • {{cite journal | vauthors = Suzuki T, Terasaki M, Takemoto-Hori C, Hanada T, Ueda T, Wada A, Watanabe K | title = Proteomic analysis of the mammalian mitochondrial ribosome. Identification of protein components in the 28 S small subunit | journal = J. Biol. Chem. | volume = 276 | issue = 35 | pages = 33181–95 | year = 2001 | pmid = 11402041 | doi = 10.1074/jbc.M103236200 }}
  • {{cite journal | vauthors = Kenmochi N, Suzuki T, Uechi T, Magoori M, Kuniba M, Higa S, Watanabe K, Tanaka T | title = The human mitochondrial ribosomal protein genes: mapping of 54 genes to the chromosomes and implications for human disorders | journal = Genomics | volume = 77 | issue = 1–2 | pages = 65–70 | year = 2001 | pmid = 11543634 | doi = 10.1006/geno.2001.6622 }}
  • {{cite journal | vauthors = Berger T, Kretzler M | title = Interaction of DAP3 and FADD only after cellular disruption | journal = Nat. Immunol. | volume = 3 | issue = 1 | pages = 3–5 | year = 2002 | pmid = 11753396 | doi = 10.1038/ni0102-3b }}
  • {{cite journal | vauthors = Hulkko SM, Zilliacus J | title = Functional interaction between the pro-apoptotic DAP3 and the glucocorticoid receptor | journal = Biochem. Biophys. Res. Commun. | volume = 295 | issue = 3 | pages = 749–55 | year = 2002 | pmid = 12099703 | doi = 10.1016/S0006-291X(02)00713-1 }}
  • {{cite journal | vauthors = Berger T, Kretzler M | title = TRAIL-induced apoptosis is independent of the mitochondrial apoptosis mediator DAP3 | journal = Biochem. Biophys. Res. Commun. | volume = 297 | issue = 4 | pages = 880–4 | year = 2002 | pmid = 12359235 | doi = 10.1016/S0006-291X(02)02310-0 }}
  • {{cite journal | vauthors = Zhang Z, Gerstein M | title = Identification and characterization of over 100 mitochondrial ribosomal protein pseudogenes in the human genome | journal = Genomics | volume = 81 | issue = 5 | pages = 468–80 | year = 2003 | pmid = 12706105 | doi = 10.1016/S0888-7543(03)00004-1 }}
  • {{cite journal | vauthors = Mukamel Z, Kimchi A | title = Death-associated protein 3 localizes to the mitochondria and is involved in the process of mitochondrial fragmentation during cell death | journal = J. Biol. Chem. | volume = 279 | issue = 35 | pages = 36732–8 | year = 2004 | pmid = 15175341 | doi = 10.1074/jbc.M400041200 }}
  • {{cite journal | vauthors = Hirota T, Obara K, Matsuda A, Akahoshi M, Nakashima K, Hasegawa K, Takahashi N, Shimizu M, Sekiguchi H, Kokubo M, Doi S, Fujiwara H, Miyatake A, Fujita K, Enomoto T, Kishi F, Suzuki Y, Saito H, Nakamura Y, Shirakawa T, Tamari M | title = Association between genetic variation in the gene for death-associated protein-3 (DAP3) and adult asthma | journal = J. Hum. Genet. | volume = 49 | issue = 7 | pages = 370–5 | year = 2004 | pmid = 15179560 | doi = 10.1007/s10038-004-0161-4 }}
  • {{cite journal | vauthors = Miyazaki T, Shen M, Fujikura D, Tosa N, Kim HR, Kon S, Uede T, Reed JC | title = Functional role of death-associated protein 3 (DAP3) in anoikis | journal = J. Biol. Chem. | volume = 279 | issue = 43 | pages = 44667–72 | year = 2004 | pmid = 15302871 | doi = 10.1074/jbc.M408101200 }}
  • {{cite journal | vauthors = Sasaki H, Ide N, Yukiue H, Kobayashi Y, Fukai I, Yamakawa Y, Fujii Y | title = Arg and DAP3 expression was correlated with human thymoma stage | journal = Clin. Exp. Metastasis | volume = 21 | issue = 6 | pages = 507–13 | year = 2004 | pmid = 15679048 | doi = 10.1007/s10585-004-2153-3 }}
{{refend}}{{Portal|Mitochondria}}
随便看

　

开放百科全书收录14589846条英语、德语、日语等多语种百科知识，基本涵盖了大多数领域的百科知识，是一部内容自由、开放的电子版国际百科全书。

　

Copyright © 2023 OENC.NET All Rights Reserved
京ICP备2021023879号 更新时间：2024/9/22 9:27:43