THE SACCHAROMYCES-CEREVISIAE SDC25 C-DOMAIN GENE-PRODUCT OVERCOMES THE DOMINANT INHIBITORY ACTIVITY OF HA-RAS ASN-17

被引：62
作者：
SCHWEIGHOFFER, F
CAI, H
CHEVALLIERMULTON, MC
FATH, I
COOPER, G
TOCOUE, B
机构：
[1] RHONE POULENC RORER,13 QUAI JULES GUESDE,BP 14,F-94403 VITRY,FRANCE
[2] HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115
[3] HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT PATHOL,BOSTON,MA 02115
来源：
MOLECULAR AND CELLULAR BIOLOGY | 1993年 / 13卷 / 01期
关键词：
D O I：
10.1128/MCB.13.1.39
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
The carboxy-terminal part of the Saccharomyces cerevisiae SDC25 gene product (SDC25 C domain) can elicit activation of mammalian Ras proteins. Specifically, SDC25 C domain functions as an exchange factor for cellular Ras proteins in CHO cells. In this study, we used the dominant inhibitory Ha-Ras Asn-17 mutant and SDC25 C domain to further investigate the interaction between cellular Ras proteins and their putative endogenous guanine nucleotide-releasing factors. Transcription from the polyomavirus thymidine kinase gene (Py tk) promoter is strongly inhibited by the expression of Ha-Ras Asn-17 in NIH 3T3 cells. Coexpression of SDC25 C domain overcomes the negative effect of the Ras mutant on the Py tk promoter. On the other hand, transactivation of the Ras-responsive element of the Py tk promoter induced by SDC25 C domain is lost upon coexpression of increasing amounts of Ha-Ras Asn-17. In addition, coexpression of SDC25 C domain overcomes the inhibition of proliferation of NIH 3T3 cells caused by Ha-Ras Asn-17. These results are consistent with the idea that the Ha-Ras Asn-17 mutant functions by titrating an upstream activator of cellular Ras proteins.
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页码：39 / 43
页数：5
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