CCN protein

CCN proteins are a family of extracellular matrix (ECM)-associated proteins involved in intercellular signaling.[1][2] Due to their dynamic role within the ECM they are considered matricellular proteins.[3][4][5]

Background

The acronym CCN is derived from the first three members of the family discovered, namely CYR61 (cysteine-rich angiogenic protein 61 or CCN1), CTGF (connective tissue growth factor or CCN2), and NOV (nephroblastoma overexpressed or CCN3). Together with three Wnt-induced secreted proteins, they comprise the CCN family of matricellular proteins. These proteins have now been renamed CCN1-6 by international consensus.[6] Members of the CCN protein family are characterized by having four conserved cysteine-rich domains, which include the insulin-like growth factor-binding domain (IGFBP), the Von Willebrand factor type C domain (VWC), the thrombospondin type 1 repeat (TSR), and a C-terminal domain (CT) with a cysteine knot motif. CCN proteins have been shown to play important roles in many cellular processes, including cell adhesion, migration, proliferation, differentiation, survival, apoptosis, and senescence. They are also involved in biological processes including angiogenesis, inflammation, fibrosis, wound healing and tumorigenesis.[1][2][7] CCN proteins likely constitute a hub for the coordination of cell signaling and communication.[8]

Members

The CCN protein family includes the following six proteins:

  • CCN1: CYR61 (cysteine-rich angiogenic protein 61)[9]
  • CCN2: CTGF (connective tissue growth factor)[10]
  • CCN3: NOV (nephroblastoma overexpressed)[11]
  • CCN4: WISP1 (WNT1 inducible signaling pathway protein-1)[1]
  • CCN5: WISP2 (WNT1 inducible signaling pathway protein-2)[12]
  • CCN6: WISP3 (WNT1 inducible signaling pathway protein-3)[13]

References
  1. Jun JI, Lau LF (December 2011). "Taking aim at the extracellular matrix: CCN proteins as emerging therapeutic targets". Nat Rev Drug Discov. 10 (12): 945–63. doi:10.1038/nrd3599. PMC 3663145. PMID 22129992.
  2. Kular L, Pakradouni J, Kitabgi P, Laurent M, Martinerie C (March 2011). "The CCN family: a new class of inflammation modulators?". Biochimie. 93 (3): 377–88. doi:10.1016/j.biochi.2010.11.010. PMID 21130134.
  3. Chen CC, Lau LF (April 2009). "Functions and mechanisms of action of CCN matricellular proteins". Int. J. Biochem. Cell Biol. 41 (4): 771–83. doi:10.1016/j.biocel.2008.07.025. PMC 2668982. PMID 18775791.
  4. Holbourn KP, Acharya KR, Perbal B (October 2008). "The CCN family of proteins: structure-function relationships". Trends Biochem. Sci. 33 (10): 461–73. doi:10.1016/j.tibs.2008.07.006. PMC 2683937. PMID 18789696.
  5. Leask A, Abraham DJ (December 2006). "All in the CCN family: essential matricellular signaling modulators emerge from the bunker". J. Cell Sci. 119 (Pt 23): 4803–10. doi:10.1242/jcs.03270. PMID 17130294.
  6. Brigstock DR, Goldschmeding R, Katsube KI, Lam SC, Lau LF, Lyons K, Naus C, Perbal B, Riser B, Takigawa M, Yeger H (April 2003). "Proposal for a unified CCN nomenclature". Mol. Pathol. 56 (2): 127–8. doi:10.1136/mp.56.2.127. PMC 1187305. PMID 12665631.
  7. Piszczatowski, Richard T.; Lents, Nathan H. (October 2016). "Regulation of the CCN genes by vitamin D: A possible adjuvant therapy in the treatment of cancer and fibrosis". Cellular Signalling. 28 (10): 1604–1613. doi:10.1016/j.cellsig.2016.07.009. ISSN 1873-3913. PMID 27460560.
  8. Perbal B (August 2013). "CCN proteins ; A Centralized Communication Network". J. Cell. Commun. Signal. 7 (3): 169–77. doi:10.1007/s12079-013-0193-7. PMC 3709049. PMID 23420091.
  9. Lau LF (October 2011). "CCN1/CYR61: the very model of a modern matricellular protein". Cell. Mol. Life Sci. 68 (19): 3149–63. doi:10.1007/s00018-011-0778-3. PMC 3651699. PMID 21805345.
  10. Hall-Glenn F, Lyons KM (October 2011). "Roles for CCN2 in normal physiological processes". Cell. Mol. Life Sci. 68 (19): 3209–17. doi:10.1007/s00018-011-0782-7. PMC 3670951. PMID 21858450.
  11. Perbal B (2006). "The CCN3 protein and cancer". Adv. Exp. Med. Biol. Advances in Experimental Medicine and Biology. 587: 23–40. doi:10.1007/978-1-4020-5133-3_3. ISBN 978-1-4020-4966-8. PMID 17163153.
  12. Russo JW, Castellot JJ (October 2010). "CCN5: biology and pathophysiology". J Cell Commun Signal. 4 (3): 119–30. doi:10.1007/s12079-010-0098-7. PMC 2948116. PMID 21063502.
  13. Huang W, Pal A, Kleer CG (March 2012). "On how CCN6 suppresses breast cancer growth and invasion". J Cell Commun Signal. 6 (1): 5–10. doi:10.1007/s12079-011-0148-9. PMC 3271195. PMID 21842227.

Further reading

Satoshi Kubota, Masaharu Takigawa (2013) CCN family acting throughout the body: recent research developments. BioMolecular Concepts. 4(5), 477–494, DOI: 10.1515/bmc-2013-0018,

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