CCN protein

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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]

Contents

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:

Related Research Articles

<span class="mw-page-title-main">Paracrine signaling</span>

Paracrine signaling is a form of cell signaling, a type of cellular communication in which a cell produces a signal to induce changes in nearby cells, altering the behaviour of those cells. Signaling molecules known as paracrine factors diffuse over a relatively short distance, as opposed to cell signaling by endocrine factors, hormones which travel considerably longer distances via the circulatory system; juxtacrine interactions; and autocrine signaling. Cells that produce paracrine factors secrete them into the immediate extracellular environment. Factors then travel to nearby cells in which the gradient of factor received determines the outcome. However, the exact distance that paracrine factors can travel is not certain.

The Wnt signaling pathways are a group of signal transduction pathways which begin with proteins that pass signals into a cell through cell surface receptors. The name Wnt is a portmanteau created from the names Wingless and Int-1. Wnt signaling pathways use either nearby cell-cell communication (paracrine) or same-cell communication (autocrine). They are highly evolutionarily conserved in animals, which means they are similar across animal species from fruit flies to humans.

<span class="mw-page-title-main">CTGF</span> Protein-coding gene in the species Homo sapiens

CTGF, also known as CCN2 or connective tissue growth factor, is a matricellular protein of the CCN family of extracellular matrix-associated heparin-binding proteins. CTGF has important roles in many biological processes, including cell adhesion, migration, proliferation, angiogenesis, skeletal development, and tissue wound repair, and is critically involved in fibrotic disease and several forms of cancers.

<span class="mw-page-title-main">Frizzled</span> Family of G-protein coupled receptor proteins

Frizzled is a family of atypical G protein-coupled receptors that serve as receptors in the Wnt signaling pathway and other signaling pathways. When activated, Frizzled leads to activation of Dishevelled in the cytosol.

<span class="mw-page-title-main">MK-886</span> Chemical compound

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<span class="mw-page-title-main">CYR61</span> Protein-coding gene in the species Homo sapiens

Cysteine-rich angiogenic inducer 61 (CYR61) or CCN family member 1 (CCN1), is a matricellular protein that in humans is encoded by the CYR61 gene.

<span class="mw-page-title-main">Frizzled-5</span> Protein-coding gene in the species Homo sapiens

Frizzled-5(Fz-5) is a protein that in humans is encoded by the FZD5 gene.

<span class="mw-page-title-main">Frizzled-7</span> Protein-coding gene in the species Homo sapiens

Frizzled-7(Fd-7) is a protein that in humans is encoded by the FZD7 gene.

<span class="mw-page-title-main">Frizzled-8</span> Protein-coding gene in the species Homo sapiens

Frizzled-8(Fz-8) is a protein that in humans is encoded by the FZD8 gene.

<span class="mw-page-title-main">Delta-like 1</span> Protein-coding gene in the species Homo sapiens

Delta-like protein 1 is a protein that in humans is encoded by the DLL1 gene.

<span class="mw-page-title-main">NOV (gene)</span> Protein-coding gene in the species Homo sapiens

NOV also known as CCN3 is a matricellular protein that in humans is encoded by the NOV gene.

<span class="mw-page-title-main">LRP6</span> Protein-coding gene in the species Homo sapiens

Low-density lipoprotein receptor-related protein 6 is a protein that in humans is encoded by the LRP6 gene. LRP6 is a key component of the LRP5/LRP6/Frizzled co-receptor group that is involved in canonical Wnt pathway.

<span class="mw-page-title-main">WIF1</span> Protein-coding gene in the species Homo sapiens

Wnt inhibitory factor 1 is a protein that in humans is encoded by the WIF1 gene. WIF1 is a lipid-binding protein that binds to Wnt proteins and prevents them from triggering signalling.

<span class="mw-page-title-main">WNT1-inducible-signaling pathway protein 1</span> Protein-coding gene in the species Homo sapiens

WNT1-inducible-signaling pathway protein 1 (WISP-1), also known as CCN4, is a matricellular protein that in humans is encoded by the WISP1 gene.

<span class="mw-page-title-main">WNT1-inducible-signaling pathway protein 3</span> Protein-coding gene in the species Homo sapiens

WNT1-inducible-signaling pathway protein 3 is a matricellular protein that in humans is encoded by the WISP3 gene.

<span class="mw-page-title-main">WNT1-inducible-signaling pathway protein 2</span> Protein-coding gene in the species Homo sapiens

WNT1-inducible-signaling pathway protein 2, or WISP-2 is a matricellular protein that in humans is encoded by the WISP2 gene.

<span class="mw-page-title-main">Cathepsin W</span> Protein-coding gene in the species Homo sapiens

Cathepsin W is a protein that in humans is encoded by the CTSW gene.

<span class="mw-page-title-main">MZF1</span> Protein-coding gene in the species Homo sapiens

Myeloid zinc finger 1 is a protein that in humans is encoded by the MZF1 gene.

Von Willebrand factor, type C is a protein domain is found in various blood plasma proteins: complement factors B, C2, CR3 and CR4; the integrins (I-domains); collagen types VI, VII, XII and XIV; and other extracellular proteins.

A matricellular protein is a dynamically expressed non-structural protein that is present in the extracellular matrix (ECM). Rather than serving as stable structural elements in the ECM, these proteins are rapidly turned over and have regulatory roles. They characteristically contain binding sites for ECM structural proteins and cell surface receptors, and may sequester and modulate activities of specific growth factors.

References

  1. 1 2 3 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. 1 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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