Open AccessIdentification of rCop-1, a New Member of the CCN Protein Family, as a Negative Regulator for Cell Transformation
Author(s) -
Rong Zhang,
Lidia Averboukh,
Weimin Zhu,
Hong Zhang,
Hakryul Jo,
Peter J. Dempsey,
Robert J. Coffey,
Arthur B. Pardee,
Liang Peng
Publication year - 1998
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.18.10.6131
Subject(s) - biology , gene , ectopic expression , gene family , regulator , oncogene , gene product , regulation of gene expression , genetics , microbiology and biotechnology , homology (biology) , gene expression , cell cycle
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.