title: Eyeing the Cyr61/CTGF/NOV (CCN) group of genes in development and diseases: highlights of their structural likenesses and functional dissimilarities.
abstract: "CCN" is an acronym referring to the first letter of each of the first three members of this original group of mammalian functionally and phylogenetically distinct extracellular matrix (ECM) proteins [i.e., cysteine-rich 61 (CYR61), connective tissue growth factor (CTGF), and nephroblastoma-overexpressed (NOV)]. Although "CCN" genes are unlikely to have arisen from a common ancestral gene, their encoded proteins share multimodular structures in which most cysteine residues are strictly conserved in their positions within several structural motifs. The CCN genes can be subdivided into members developmentally indispensable for embryonic viability (e.g., CCN1, 2 and 5), each assuming unique tissue-specific functions, and members not essential for embryonic development (e.g., CCN3, 4 and 6), probably due to a balance of functional redundancy and specialization during evolution. The temporo-spatial regulation of the CCN genes and the structural information contained within the sequences of their encoded proteins reflect diversity in their context and tissue-specific functions. Genetic association studies and experimental anomalies, replicated in various animal models, have shown that altered CCN gene structure or expression is associated with "injury" stimuli--whether mechanical (e.g., trauma, shear stress) or chemical (e.g., ischemia, hyperglycemia, hyperlipidemia, inflammation). Consequently, increased organ-specific susceptibility to structural damages ensues. These data underscore the critical functions of CCN proteins in the dynamics of tissue repair and regeneration and in the compensatory responses preceding organ failure. A better understanding of the regulation and mode of action of each CCN member will be useful in developing specific gain- or loss-of-function strategies for therapeutic purposes.
authors.affiliation: Department of Cell Biology, Downstate Medical Center, Brooklyn, NY, 11203, USA.|Department of Ophthalmology, Downstate Medical Center, Brooklyn, NY, 11203, USA.
authors.forename: Izabela
authors.initials: I
authors.lastname: Krupska
authors.affiliation: HUGO Gene Nomenclature Committee, European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, CB10 1SD, UK.
authors.forename: Elspeth A
authors.initials: EA
authors.lastname: Bruford
authors.affiliation: Department of Cell Biology, Downstate Medical Center, Brooklyn, NY, 11203, USA. bchaqour@downstate.edu.|Department of Ophthalmology, Downstate Medical Center, Brooklyn, NY, 11203, USA. bchaqour@downstate.edu.|State University of New York (SUNY) Eye Institute Downstate Medical Center, 450 Clarkson Avenue, MSC 5, Brooklyn, NY, 11203, USA. bchaqour@downstate.edu.
authors.forename: Brahim
authors.initials: B
authors.lastname: Chaqour
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D055511:CCN Intercellular Signaling Proteins / Q000145:classification / Q000235:genetics* / Q000502:physiology; D004194:Disease / Q000209:etiology / Q000235:genetics; D005091:Exons; D018507:Gene Expression Regulation, Developmental; D020022:Genetic Predisposition to Disease; D006801:Humans; D007438:Introns; D008969:Molecular Sequence Data
chemical_list: D055511:CCN Intercellular Signaling Proteins