sel-11 and cdc-42, two negative modulators of LIN-12/Notch activity in C. elegans.
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.
Choi
Min Sung
MS
Department of Biological Sciences, Howard Hughes Medical Institute, Columbia University College of Physicians and Surgeons, New York, New York, United States of America.
Yoo
Andrew S
AS
Greenwald
Iva
I
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
D029742:Caenorhabditis elegans Proteins; C082460:Lin-12 protein, C elegans; D008565:Membrane Proteins; D051880:Receptors, Notch