sel-11 and cdc-42, two negative modulators of LIN-12/notch activity in C. elegans

Min Sung Choi, Andrew S. Yoo, Iva Greenwald

Research output: Contribution to journalArticle

7 Scopus citations

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. Methodology/Principal Findings: 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/Significance: 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.

Original languageEnglish
Article numbere11885
JournalPloS one
Volume5
Issue number7
DOIs
StatePublished - Aug 20 2010
Externally publishedYes

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