“ADAM15”的意思、由来-开放百科全书

Function

The protein encoded by this gene is a member of the ADAM (a disintegrin and metalloproteinase) protein family. ADAM family members are type I transmembrane glycoproteins known to be involved in cell adhesion and proteolytic ectodomain processing of cytokines and adhesion molecules. This protein contains multiple functional domains including a zinc-binding metalloprotease domain, a disintegrin-like domain, as well as an EGF-like domain. Through its disintegrin-like domain, this protein specifically interacts with the integrin beta chain, beta 3. It also interacts with Src family protein-tyrosine kinases in a phosphorylation-dependent manner, suggesting that this protein may function in cell-cell adhesion as well as in cellular signaling. Multiple alternatively spliced transcript variants encoding distinct isoforms have been observed.^[2]

Clinical significance

Arthritis

ADAM15 has been associated with a number of diseases, most recently Rheumatoid Arthritis where it is required for the activation of the FAK and Src pathways to generate apoptosis resistance in response to apoptotic signalling or cell stress.^[3] ADAM15 also has an antiapoptotic effect in osteoarthritic chondrocytes.^[4]

Cancer

The precise role of ADAM15 in cancer is still unclear but the metalloprotein has been linked to a number of different cancerous diseases such as Breast cancer where the expression of the protein is increased in carcinoma in-situ, invasive carcinoma and metastatic breast cancer tissues^[5] Additionally, the alternative splice variant forms of ADAM15 have also been correlated with different prognosis in 48 breast cancer patients based upon their expression levels.^[6] ADAM15 has also been shown to have a role in Prostate Cancer again through increased expression in neoplastic and metastatic tissues compared to normal prostate tissues^[5] and also through its modulation of epithelial cell- tumour cell interactions.^[6]

Interactions

The alternatively spliced isoforms have also been shown to exhibit different preferential interactions with proteins containing SH3 domains.^[9]^[10]

References

1. ^{{cite journal | vauthors = Zhang XP, Kamata T, Yokoyama K, Puzon-McLaughlin W, Takada Y | title = Specific interaction of the recombinant disintegrin-like domain of MDC-15 (metargidin, ADAM-15) with integrin alphavbeta3 | journal = J Biol Chem | volume = 273 | issue = 13 | pages = 7345–50 |date=April 1998| pmid = 9516430 | pmc = | doi =10.1074/jbc.273.13.7345 }}
2. ^{{cite web | title = Entrez Gene: ADAM15 ADAM metallopeptidase domain 15 (metargidin)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8751| accessdate = }}
3. ^{{cite journal | vauthors = Böhm BB, Freund I, Krause K, Kinne RW, Burkhardt H | title = ADAM15 adds to apoptosis resistance of synovial fibroblasts by modulating focal adhesion kinase signaling | journal = Arthritis Rheum. | volume = 65 | issue = 11 | pages = 2826–34 |date=November 2013 | pmid = 23918525 | doi = 10.1002/art.38109 }}
4. ^{{cite journal | vauthors = Böhm B, Hess S, Krause K, Schirner A, Ewald W, Aigner T, Burkhardt H | title = ADAM15 exerts an antiapoptotic effect on osteoarthritic chondrocytes via up-regulation of the X-linked inhibitor of apoptosis | journal = Arthritis Rheum. | volume = 62 | issue = 5 | pages = 1372–82 |date=May 2010 | pmid = 20213810 | doi = 10.1002/art.27387 }}
5. ^¹{{cite journal | vauthors = Kuefer R, Day KC, Kleer CG, Sabel MS, Hofer MD, Varambally S, Zorn CS, Chinnaiyan AM, Rubin MA, Day ML | title = ADAM15 disintegrin is associated with aggressive prostate and breast cancer disease | journal = Neoplasia | volume = 8 | issue = 4 | pages = 319–29 |date=April 2006 | pmid = 16756724 | pmc = 1600681 | doi = 10.1593/neo.05682 | url = }}
6. ^{{cite journal | vauthors = Najy AJ, Day KC, Day ML | title = ADAM15 supports prostate cancer metastasis by modulating tumor cell-endothelial cell interaction | journal = Cancer Res. | volume = 68 | issue = 4 | pages = 1092–9 |date=February 2008 | pmid = 18281484 | doi = 10.1158/0008-5472.CAN-07-2432 }}
7. ^¹²{{cite journal | date = February 2002 | vauthors = Poghosyan Z, Robbins SM, Houslay MD, Webster A, Murphy G, Edwards DR | title = Phosphorylation-dependent interactions between ADAM15 cytoplasmic domain and Src family protein-tyrosine kinases | journal = J. Biol. Chem. | volume = 277 | issue = 7 | pages = 4999–5007 | pmid = 11741929 | doi = 10.1074/jbc.M107430200}}
8. ^¹{{cite journal | date = October 1999 | vauthors = Howard L, Nelson KK, Maciewicz RA, Blobel CP | title = Interaction of the metalloprotease disintegrins MDC9 and MDC15 with two SH3 domain-containing proteins, endophilin I and SH3PX1 | journal = J. Biol. Chem. | volume = 274 | issue = 44 | pages = 31693–9 | pmid = 10531379 | doi = 10.1074/jbc.274.44.31693}}
9. ^¹{{cite journal | vauthors = Zhong JL, Poghosyan Z, Pennington CJ, Scott X, Handsley MM, Warn A, Gavrilovic J, Honert K, Krüger A, Span PN, Sweep FC, Edwards DR | title = Distinct functions of natural ADAM-15 cytoplasmic domain variants in human mammary carcinoma | journal = Mol. Cancer Res. | volume = 6 | issue = 3 | pages = 383–94 |date=March 2008 | pmid = 18296648 | doi = 10.1158/1541-7786.MCR-07-2028 }}
10. ^{{cite journal | vauthors = Kleino I, Ortiz RM, Yritys M, Huovila AP, Saksela K | title = Alternative splicing of ADAM15 regulates its interactions with cellular SH3 proteins | journal = J. Cell. Biochem. | volume = 108 | issue = 4 | pages = 877–85 |date=November 2009 | pmid = 19718658 | doi = 10.1002/jcb.22317 }}