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A component of the transcriptional mediator complex inhibits RAS-dependent vulval fate specification in C. elegans

Moghal, Nadeem and Sternberg, Paul W. (2003) A component of the transcriptional mediator complex inhibits RAS-dependent vulval fate specification in C. elegans. Development, 130 (1). pp. 57-69. ISSN 0950-1991. http://resolver.caltech.edu/CaltechAUTHORS:MOGdev03a

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Abstract

Negative regulation of receptor tyrosine kinase (RTK)/RAS signaling pathways is important for normal development and the prevention of disease in humans. We have used a genetic screen in C. elegans to identify genes that antagonize the activity of activated LET-23, a member of the EGFR family of RTKs. We identified two loss-of-function mutations in dpy-22, previously cloned as sop-1, that promote the ability of activated LET-23 to induce ectopic vulval fates. DPY-22 is a glutamine-rich protein that is most similar to human TRAP230, a component of a transcriptional mediator complex. DPY-22 has previously been shown to regulate WNT responses through inhibition of the ß-catenin-like protein BAR-1. We provide evidence that DPY-22 also inhibits RAS-dependent vulval fate specification independently of BAR-1, and probably regulates the activities of multiple transcription factors during development. Furthermore, we demonstrate that although inhibition of BAR-1-dependent gene expression has been shown to require the C-terminal glutamine-rich region, this region is dispensable for inhibition of RAS-dependent cell differentiation. Thus, the glutamine-rich region contributes to specificity of this class of mediator protein.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1242/10.1242/dev.00189DOIUNSPECIFIED
http://dev.biologists.org/cgi/content/abstract/130/1/57PublisherUNSPECIFIED
Additional Information:Copyright © 2003 The Company of Biologists Limited. Accepted 4 October 2002. Some nematode strains used in this work were provided by the Caenorhabditis Genetics Center, which is funded by the NIH National Center for Research Resources (NCRR). We thank S. Emmons and C. Kenyon for providing strains, and A. Fire for plasmids. We thank J. Maloof and C. Kenyon for help in identifying the bar-1(mu63) mutation; H. Sawa for communicating unpublished results; and L.R. Garcia, R. Lee, B.P. Gupta, H. Yu, G. Schindelman and C. Van Buskirk for helpful discussions. This research was supported by the Howard Hughes Medical Institute, of which P.W.S. is an investigator. N.M. was supported by postdoctoral fellowships from the Leukemia and Lymphoma Society, and the California Breast Cancer Research Program.
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Funding AgencyGrant Number
Howard Hughes Medical InstituteUNSPECIFIED
Leukemia and Lymphoma SocietyUNSPECIFIED
California Breast Cancer Research ProgramUNSPECIFIED
Subject Keywords:EGF, RAS, LET-23, SOP-1, DPY-22, Mediator, Vulva, C. elegans
Record Number:CaltechAUTHORS:MOGdev03a
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:MOGdev03a
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:12898
Collection:CaltechAUTHORS
Deposited By: Archive Administrator
Deposited On:09 Jan 2009 07:42
Last Modified:26 Dec 2012 10:41

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