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词条 WNT1-inducible-signaling pathway protein 1
释义

  1. Structure

  2. Role in bone development

  3. Clinical significance

  4. References

{{Infobox_gene}}WNT1-inducible-signaling pathway protein 1 (WISP-1),[1] also known as CCN4, is a matricellular protein that in humans is encoded by the WISP1 gene.[2][3]

Structure

WISP-1 is highly homologous to CYR61 (CCN1) and CTGF (CCN2), and is a member of the CCN family of secreted, extracellular matrix (ECM)-associated signaling proteins (CCN intercellular signaling protein). The CCN family of proteins shares a common molecular protein structure, characterized by an N-terminal secretory signal peptide followed by four distinct domains with homologies to insulin-like growth factor binding protein (IGFBP), von Willebrand type C repeats (vWC), thrombospondin type 1 repeat (TSR), and a cysteine knot motif within the C-terminal (CT) domain. This family of proteins regulates diverse cellular functions, including cell adhesion, migration, proliferation, differentiation, and survival.[1][4][5][6]

Role in bone development

WISP-1 promotes mesenchymal cell proliferation and osteoblastic differentiation, and represses chondrocytic differentiation.[7] WISP-1 binds BMP2 and enhances BMP2 function in osteogenesis.[8] These activities may be modulated by its direct binding to decorin and biglycan,[9] two members of a family of small leucine-rich proteoglycans present in the extracellular matrix of connective tissue.

Clinical significance

WISP-1 attenuates p53-mediated apoptosis in response to DNA damage through activation of the Akt kinase,[10] and inhibits TNF-induced cell death in cardiomyocytes.[11] Recombinant WISP-1 enhances ECM deposition in human fibroblasts, suggesting that it might play a role in matrix remodeling in vivo. WISP-1 is upregulated in human patients with idiopathic pulmonary fibrosis and in a mouse model of bleomycin-induced lung fibrosis.[12] Orotracheal application of WISP-1 neutralizing antibodies to the lung ameliorates bleomycin-induced lung fibrosis,[12] raising the possibility that WISP-1 might be a potential target for anti-fibrotic therapy.[1]

Expression of WISP-1 promotes tumor growth,[13] and high WISP-1 expression correlates with advanced tumors of the brain, breast, colon, and lung.[14][15][16][17] WISP-1 appears to inhibit metastasis[18][19] although expression of a WISP-1 splicing variant lacking the VWC domain appears to enhance the invasive characteristic of gastric carcinoma cells.[20]

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References

1. ^1 2 {{cite journal | vauthors = Jun JI, Lau LF | title = Taking aim at the extracellular matrix: CCN proteins as emerging therapeutic targets | journal = Nature Reviews. Drug Discovery | volume = 10 | issue = 12 | pages = 945–63 | date = Dec 2011 | pmid = 22129992 | doi = 10.1038/nrd3599 | pmc = 3663145 }}
2. ^{{cite journal | vauthors = Pennica D, Swanson TA, Welsh JW, Roy MA, Lawrence DA, Lee J, Brush J, Taneyhill LA, Deuel B, Lew M, Watanabe C, Cohen RL, Melhem MF, Finley GG, Quirke P, Goddard AD, Hillan KJ, Gurney AL, Botstein D, Levine AJ | title = WISP genes are members of the connective tissue growth factor family that are up-regulated in wnt-1-transformed cells and aberrantly expressed in human colon tumors | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 95 | issue = 25 | pages = 14717–22 | date = Dec 1998 | pmid = 9843955 | pmc = 24515 | doi = 10.1073/pnas.95.25.14717 }}
3. ^{{cite web | title = Entrez Gene: WISP1 WNT1 inducible signaling pathway protein 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8840| accessdate = }}
4. ^{{cite journal | vauthors = Chen CC, Lau LF | title = Functions and mechanisms of action of CCN matricellular proteins | journal = The International Journal of Biochemistry & Cell Biology | volume = 41 | issue = 4 | pages = 771–83 | date = Apr 2009 | pmid = 18775791 | pmc = 2668982 | doi = 10.1016/j.biocel.2008.07.025 }}
5. ^{{cite journal | vauthors = Holbourn KP, Acharya KR, Perbal B | title = The CCN family of proteins: structure-function relationships | journal = Trends in Biochemical Sciences | volume = 33 | issue = 10 | pages = 461–73 | date = Oct 2008 | pmid = 18789696 | pmc = 2683937 | doi = 10.1016/j.tibs.2008.07.006 }}
6. ^{{cite journal | vauthors = Leask A, Abraham DJ | title = All in the CCN family: essential matricellular signaling modulators emerge from the bunker | journal = Journal of Cell Science | volume = 119 | issue = Pt 23 | pages = 4803–10 | date = Dec 2006 | pmid = 17130294 | doi = 10.1242/jcs.03270 }}
7. ^{{cite journal | vauthors = French DM, Kaul RJ, D'Souza AL, Crowley CW, Bao M, Frantz GD, Filvaroff EH, Desnoyers L | title = WISP-1 is an osteoblastic regulator expressed during skeletal development and fracture repair | journal = The American Journal of Pathology | volume = 165 | issue = 3 | pages = 855–67 | date = Sep 2004 | pmid = 15331410 | pmc = 1618601 | doi = 10.1016/S0002-9440(10)63348-2 }}
8. ^{{cite journal | vauthors = Ono M, Inkson CA, Kilts TM, Young MF | title = WISP-1/CCN4 regulates osteogenesis by enhancing BMP-2 activity | journal = Journal of Bone and Mineral Research | volume = 26 | issue = 1 | pages = 193–208 | date = Jan 2011 | pmid = 20684029 | pmc = 3179320 | doi = 10.1002/jbmr.205 }}
9. ^{{cite journal | vauthors = Desnoyers L, Arnott D, Pennica D | title = WISP-1 binds to decorin and biglycan | journal = The Journal of Biological Chemistry | volume = 276 | issue = 50 | pages = 47599–607 | date = Dec 2001 | pmid = 11598131 | doi = 10.1074/jbc.M108339200 }}
10. ^{{cite journal | vauthors = Su F, Overholtzer M, Besser D, Levine AJ | title = WISP-1 attenuates p53-mediated apoptosis in response to DNA damage through activation of the Akt kinase | journal = Genes & Development | volume = 16 | issue = 1 | pages = 46–57 | date = Jan 2002 | pmid = 11782444 | pmc = 155313 | doi = 10.1101/gad.942902 }}
11. ^{{cite journal | vauthors = Venkatachalam K, Venkatesan B, Valente AJ, Melby PC, Nandish S, Reusch JE, Clark RA, Chandrasekar B | title = WISP1, a pro-mitogenic, pro-survival factor, mediates tumor necrosis factor-alpha (TNF-alpha)-stimulated cardiac fibroblast proliferation but inhibits TNF-alpha-induced cardiomyocyte death | journal = The Journal of Biological Chemistry | volume = 284 | issue = 21 | pages = 14414–27 | date = May 2009 | pmid = 19339243 | pmc = 2682890 | doi = 10.1074/jbc.M809757200 }}
12. ^1 {{cite journal | vauthors = Königshoff M, Kramer M, Balsara N, Wilhelm J, Amarie OV, Jahn A, Rose F, Fink L, Seeger W, Schaefer L, Günther A, Eickelberg O | title = WNT1-inducible signaling protein-1 mediates pulmonary fibrosis in mice and is upregulated in humans with idiopathic pulmonary fibrosis | journal = The Journal of Clinical Investigation | volume = 119 | issue = 4 | pages = 772–87 | date = Apr 2009 | pmid = 19287097 | pmc = 2662540 | doi = 10.1172/JCI33950 }}
13. ^{{cite journal | vauthors = Xu L, Corcoran RB, Welsh JW, Pennica D, Levine AJ | title = WISP-1 is a Wnt-1- and beta-catenin-responsive oncogene | journal = Genes & Development | volume = 14 | issue = 5 | pages = 585–95 | date = Mar 2000 | pmid = 10716946 | pmc = 316421 | doi = }}
14. ^{{cite journal | vauthors = Kim Y, Kim KH, Lee J, Lee YA, Kim M, Lee SJ, Park K, Yang H, Jin J, Joo KM, Lee J, Nam DH | title = Wnt activation is implicated in glioblastoma radioresistance | journal = Laboratory Investigation | volume = 92 | issue = 3 | pages = 466–73 | date = Mar 2012 | pmid = 22083670 | doi = 10.1038/labinvest.2011.161 }}
15. ^{{cite journal | vauthors = Xie D, Nakachi K, Wang H, Elashoff R, Koeffler HP | title = Elevated levels of connective tissue growth factor, WISP-1, and CYR61 in primary breast cancers associated with more advanced features | journal = Cancer Research | volume = 61 | issue = 24 | pages = 8917–23 | date = Dec 2001 | pmid = 11751417 | doi = }}
16. ^{{cite journal | vauthors = Tian C, Zhou ZG, Meng WJ, Sun XF, Yu YY, Li L, Luo HZ, Yang L, Zhou B, Gu J | title = Overexpression of connective tissue growth factor WISP-1 in Chinese primary rectal cancer patients | journal = World Journal of Gastroenterology | volume = 13 | issue = 28 | pages = 3878–82 | date = Jul 2007 | pmid = 17657846 | doi = 10.3748/wjg.v13.i28.3878 }}
17. ^{{cite journal | vauthors = Chen PP, Li WJ, Wang Y, Zhao S, Li DY, Feng LY, Shi XL, Koeffler HP, Tong XJ, Xie D | title = Expression of Cyr61, CTGF, and WISP-1 correlates with clinical features of lung cancer | journal = PLOS ONE | volume = 2 | issue = 6 | pages = e534 | year = 2007 | pmid = 17579708 | pmc = 1888724 | doi = 10.1371/journal.pone.0000534 }} {{open access}}
18. ^{{cite journal | vauthors = Hashimoto Y, Shindo-Okada N, Tani M, Nagamachi Y, Takeuchi K, Shiroishi T, Toma H, Yokota J | title = Expression of the Elm1 gene, a novel gene of the CCN (connective tissue growth factor, Cyr61/Cef10, and neuroblastoma overexpressed gene) family, suppresses In vivo tumor growth and metastasis of K-1735 murine melanoma cells | journal = The Journal of Experimental Medicine | volume = 187 | issue = 3 | pages = 289–96 | date = Feb 1998 | pmid = 9449709 | pmc = 2212122 | doi = 10.1084/jem.187.3.289 }}
19. ^{{cite journal | vauthors = Soon LL, Yie TA, Shvarts A, Levine AJ, Su F, Tchou-Wong KM | title = Overexpression of WISP-1 down-regulated motility and invasion of lung cancer cells through inhibition of Rac activation | journal = The Journal of Biological Chemistry | volume = 278 | issue = 13 | pages = 11465–70 | date = Mar 2003 | pmid = 12529380 | doi = 10.1074/jbc.M210945200 }}
20. ^{{cite journal | vauthors = Tanaka S, Sugimachi K, Saeki H, Kinoshita J, Ohga T, Shimada M, Maehara Y, Sugimachi K | title = A novel variant of WISP1 lacking a Von Willebrand type C module overexpressed in scirrhous gastric carcinoma | journal = Oncogene | volume = 20 | issue = 39 | pages = 5525–32 | date = Sep 2001 | pmid = 11571650 | doi = 10.1038/sj.onc.1204723 }}

1 : CCN proteins
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