Biology:WNT1-inducible-signaling pathway protein 3
 Generic protein structure example |
WNT1-inducible-signaling pathway protein 3[1][2] (WISP3, also named CCN6) is a matricellular protein that in humans is encoded by the WISP3 gene.
Structure
It is a member of the CCN family (CCN intercellular signaling protein) of secreted, extracellular matrix (ECM)-associated signaling matricellular proteins. The CCN acronym is derived from the first three members of the family identified, namely CYR61 (cysteine-rich angiogenic inducer 61, or CCN1), CTGF (connective tissue growth factor, or CCN2), and NOV (nephroblastoma overexpressed, or CCN3). These proteins, together with WISP1 (CCN4), and WISP2 (CCN5) comprise the six-member CCN family in vertebrates. CCN proteins characteristically contain an N-terminal secretory signal peptide followed by four structurally 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.
Function
The CCN family of proteins regulates diverse cellular functions, including cell adhesion, migration, proliferation, survival, and differentiation.[3][4][5]
Clinical significance
Mutations in the human WISP3 gene are associated with progressive pseudorheumatoid dysplasia, a juvenile onset autosomal recessive skeletal disorder, indicating that the gene is essential for normal postnatal skeletal growth and cartilage homeostasis.[6] However, mice with WISP3 knockout or overexpression are normal and suffer no apparent developmental defect.[7][8] Loss of WISP3 expression is associated with aggressive inflammatory breast cancer and breast cancer with axillary lymph node metastasis, suggesting that WISP3/CCN6 may function as a suppressor of breast cancer growth and metastasis.[2]
References
- ↑ "Taking aim at the extracellular matrix: CCN proteins as emerging therapeutic targets". Nat Rev Drug Discov 10 (12): 945–63. December 2011. doi:10.1038/nrd3599. PMID 22129992.
- ↑ 2.0 2.1 "On how CCN6 suppresses breast cancer growth and invasion". J Cell Commun Signal 6 (1): 5–10. March 2012. doi:10.1007/s12079-011-0148-9. PMID 21842227.
- ↑ "Functions and mechanisms of action of CCN matricellular proteins". Int. J. Biochem. Cell Biol. 41 (4): 771–83. April 2009. doi:10.1016/j.biocel.2008.07.025. PMID 18775791.
- ↑ "The CCN family of proteins: structure-function relationships". Trends Biochem. Sci. 33 (10): 461–73. October 2008. doi:10.1016/j.tibs.2008.07.006. PMID 18789696.
- ↑ "All in the CCN family: essential matricellular signaling modulators emerge from the bunker". J. Cell Sci. 119 (Pt 23): 4803–10. December 2006. doi:10.1242/jcs.03270. PMID 17130294.
- ↑ "Mutations in the CCN gene family member WISP3 cause progressive pseudorheumatoid dysplasia". Nat. Genet. 23 (1): 94–8. September 1999. doi:10.1038/12699. PMID 10471507.
- ↑ "WISP3, the gene responsible for the human skeletal disease progressive pseudorheumatoid dysplasia, is not essential for skeletal function in mice". Mol. Cell. Biol. 25 (1): 414–21. January 2005. doi:10.1128/MCB.25.1.414-421.2005. PMID 15601861.
- ↑ "Normal growth and development in mice over-expressing the CCN family member WISP3". J Cell Commun Signal 3 (2): 105–13. June 2009. doi:10.1007/s12079-009-0040-z. PMID 19401829.
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