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PMID: 8380225 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

The Saccharomyces cerevisiae SDC25 C-domain gene product overcomes the dominant inhibitory activity of Ha-Ras Asn-17.

Molecular and cellular biology ·Vol. 13 ·No. 1 ·1993-01-00 ·Pages 39-43

Schweighoffer F, Cai H, Chevallier-Multon MC, Fath I, Cooper G, Tocque B

Abstract

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.

Related Genes
SDC25
MeSH Terms
3T3 Cells Animals Cell Division Enhancer Elements, Genetic Fungal Proteins/metabolism GTP-Binding Proteins/metabolism Gene Expression Regulation Genes, Dominant Genes, ras Guanine Nucleotides/metabolism Mice Polyomavirus/genetics Proto-Oncogene Proteins p21(ras)/metabolism Recombinant Proteins/metabolism Saccharomyces cerevisiae/genetics Structure-Activity Relationship Transcription, Genetic Transfection rap GTP-Binding Proteins
Chemicals
Fungal Proteins Guanine Nucleotides Recombinant Proteins GTP-Binding Proteins Proto-Oncogene Proteins p21(ras) rap GTP-Binding Proteins
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Schweighoffer F
Dana-Farber Cancer Institute, Boston, Massachusetts.
Cai H
Chevallier-Multon M C
Fath I
Cooper G
Tocque B
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39 references, click to expand
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/mcb.13.1.39-43.1993
Published
1993-01-00
Pages
39-43
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC358882
Subset
IM
Grants
NCI NIH HHS · R0I CAI8689 · United States
External Links
PubMed source DOI: 10.1128/mcb.13.1.39-43.1993 PMC Full Text View journal details
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