title: sel-11 and cdc-42, two negative modulators of LIN-12/Notch activity in C. elegans.
abstract: BACKGROUND
  LIN-12/Notch signaling is important for cell-cell interactions during development, and mutations resulting in constitutive LIN-12/Notch signaling can cause cancer. Loss of negative regulators of lin-12/Notch activity has the potential for influencing cell fate decisions during development and the genesis or aggressiveness of cancer.
  
  
  RESULTS
  We describe two negative modulators of lin-12 activity in C. elegans. One gene, sel-11, was initially defined as a suppressor of a lin-12 hypomorphic allele; the other gene, cdc-42, is a well-studied Rho GTPase. Here, we show that SEL-11 corresponds to yeast Hrd1p and mammalian Synoviolin. We also show that cdc-42 has the genetic properties consistent with negative regulation of lin-12 activity during vulval precursor cell fate specification.
  
  
  CONCLUSIONS
  Our results underscore the multiplicity of negative regulatory mechanisms that impact on lin-12/Notch activity and suggest novel mechanisms by which constitutive lin-12/Notch activity might be exacerbated in cancer.
authors.affiliation: Department of Biological Sciences, Howard Hughes Medical Institute, Columbia University College of Physicians and Surgeons, New York, New York, United States of America.
authors.forename: Min Sung
authors.initials: MS
authors.lastname: Choi
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Yoo
authors.forename: Iva
authors.initials: I
authors.lastname: Greenwald
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D034622:RNA Interference; D051880:Receptors, Notch
chemical_list: D029742:Caenorhabditis elegans Proteins; C082460:Lin-12 protein, C elegans; D008565:Membrane Proteins; D051880:Receptors, Notch