Identification of rCop-1, a new member of the CCN protein family, as a negative regulator for cell transformation.
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.
Zhang
R
R
Vanderbilt Cancer Center, Department of Cell Biology, Vanderbilt University, Nashville, Tennessee 37232, USA.
Averboukh
L
L
Zhu
W
W
Zhang
H
H
Jo
H
H
Dempsey
P J
PJ
Coffey
R J
RJ
Pardee
A B
AB
Liang
P
P
D000375:Aging; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D055511:CCN Intercellular Signaling Proteins; D015197:Carcinogenicity Tests; D002453:Cell Cycle; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D005347:Fibroblasts / Q000378:metabolism; D015870:Gene Expression; D005814:Genes, Viral; D016158:Genes, p53; D011905:Genes, ras; D051379:Mice; D008969:Molecular Sequence Data; D051381:Rats; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D012190:Retroviridae / Q000235:genetics; D012377:Rodentia / Q000196:embryology; D017386:Sequence Homology, Amino Acid; D013347:Subcellular Fractions
D055511:CCN Intercellular Signaling Proteins; C115044:CCN5 protein, rat; D012097:Repressor Proteins