Identification of rCop-1, a new member of the CCN protein family, as a negative regulator for cell transformation.

Zhang R, Averboukh L, Zhu W, Zhang H, Jo H, Dempsey PJ, Coffey RJ, Pardee AB, Liang P
Mol Cell Biol. 1998 18 (10): 6131-41

PMID: 9742130 · PMCID: PMC109199 · DOI:10.1128/mcb.18.10.6131

By using a model system for cell transformation mediated by the cooperation of the activated H-ras oncogene and the inactivated p53 tumor suppressor gene, rCop-1 was identified by mRNA differential display as a gene whose expression became lost after cell transformation. Homology analysis indicates that rCop-1 belongs to an emerging cysteine-rich growth regulator family called CCN, which includes connective-tissue growth factor, CYR61, CEF10 (v-src inducible), and the product of the nov proto-oncogene. Unlike the other members of the CCN gene family, rCop-1 is not an immediate-early gene, it lacks the conserved C-terminal domain which was shown to confer both growth-stimulating and heparin-binding activities, and its expression is lost in cells transformed by a variety of mechanisms. Ectopic expression of rCop-1 by retroviral gene transfers led to cell death in a transformation-specific manner. These results suggest that rCop-1 represents a new class of CCN family proteins that have functions opposing those of the previously identified members.

MeSH Terms (23)

Aging Amino Acid Sequence Animals Apoptosis Base Sequence Carcinogenicity Tests CCN Intercellular Signaling Proteins Cell Cycle Cell Line Cell Transformation, Neoplastic Fibroblasts Gene Expression Genes, p53 Genes, ras Genes, Viral Mice Molecular Sequence Data Rats Repressor Proteins Retroviridae Rodentia Sequence Homology, Amino Acid Subcellular Fractions

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