CCN protein explained

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]

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,

Notes and References

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