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Molecular and Cellular Biology, October 1998, p. 6131-6141, Vol. 18, No. 10
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Identification of rCop-1, a New Member of the CCN Protein Family, as a Negative Regulator for Cell Transformation

Rong Zhang,1 Lidia Averboukh,2 Weimin Zhu,2 Hong Zhang,1 Hakryul Jo,1 Peter J. Dempsey,1 Robert J. Coffey,1 Arthur B. Pardee,2 and Peng Liang1,*

Vanderbilt Cancer Center, Department of Cell Biology, Vanderbilt University, Nashville, Tennessee 37232,1 and Division of Cell Growth and Regulation, Dana-Farber Cancer Institute, Boston, Massachusetts 021152

Received 22 January 1998/Returned for modification 2 March 1998/Accepted 20 July 1998

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.

* Corresponding author. Mailing address: Vanderbilt Cancer Center, Department of Cell Biology, Vanderbilt University, 658 Medical Research Building II, Nashville, TN 37232. Phone: (615) 936-2182. Fax: (615) 936-2183. E-mail: peng.liang{at}mcmail.vanderbilt.edu.

Molecular and Cellular Biology, October 1998, p. 6131-6141, Vol. 18, No. 10
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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