title: A component of the transcriptional mediator complex inhibits RAS-dependent vulval fate specification in C. elegans.
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 beta-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.
authors.affiliation: Howard Hughes Medical Institute, and Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Nadeem
authors.initials: N
authors.lastname: Moghal
authors.forename: Paul W
authors.initials: PW
authors.lastname: Sternberg
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000254:growth & development; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D012734:Disorders of Sex Development / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005973:Glutamine; D015801:Helminth Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D009154:Mutation; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014844:Vulva / Q000002:abnormalities / Q000166:cytology / Q000254:growth & development*; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D015801:Helminth Proteins; C117260:Pry-1 protein, C elegans; D014157:Transcription Factors; C115014:bar-1 protein, C elegans; C413707:dpy-22 protein, C elegans; D005973:Glutamine; C066646:let-60 protein, C elegans; D066246:ErbB Receptors; C085873:let-23 protein, C elegans; D018631:ras Proteins