Abstract
Mutations that influence lin-12 activity in Caenorhabditis elegans may identify conserved factors that regulate the activity of lin-12/Notch proteins. We describe genetic evidence indicating that sel-10 is a negative regulator of lin-12/Notch-mediated signaling in C. elegans. Sequence analysis shows that SEL-10 is a member of the CDC4 family of proteins and has a potential human ortholog. Coimmunoprecipitation data indicate that C. elegans SEL-10 complexes with LIN-12 and with murine Notch4. We propose that SEL-10 promotes the ubiquitin-mediated turnover of LIN-12/Notch proteins, and discuss potential roles for the regulation of lin-12/Notch activity by sel-10 in cell fate decisions and tumorigenesis.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, Non-P.H.S.
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Amino Acid Sequence
-
Animals
-
Base Sequence
-
Caenorhabditis elegans / genetics
-
Caenorhabditis elegans / metabolism*
-
Caenorhabditis elegans Proteins*
-
Cell Cycle Proteins / chemistry
-
Cell Cycle Proteins / genetics
-
Cell Cycle Proteins / metabolism*
-
Cell Differentiation / physiology
-
Cell Transformation, Neoplastic
-
Cloning, Molecular
-
DNA, Complementary
-
F-Box Proteins*
-
F-Box-WD Repeat-Containing Protein 7
-
Gene Dosage
-
Genes, Helminth
-
Helminth Proteins / chemistry
-
Helminth Proteins / genetics
-
Helminth Proteins / metabolism*
-
Humans
-
Membrane Proteins / genetics
-
Membrane Proteins / metabolism*
-
Mice
-
Molecular Sequence Data
-
Mutation
-
Proto-Oncogene Proteins / genetics
-
Proto-Oncogene Proteins / metabolism
-
Receptor, Notch4
-
Receptors, Cell Surface*
-
Receptors, Notch
-
Sequence Homology, Amino Acid
-
Signal Transduction
-
Ubiquitin-Protein Ligases*
-
Ubiquitins / metabolism
Substances
-
Caenorhabditis elegans Proteins
-
Cell Cycle Proteins
-
DNA, Complementary
-
F-Box Proteins
-
F-Box-WD Repeat-Containing Protein 7
-
FBXW7 protein, human
-
Fbxw7 protein, mouse
-
Helminth Proteins
-
Lin-12 protein, C elegans
-
Membrane Proteins
-
NOTCH4 protein, human
-
Proto-Oncogene Proteins
-
Receptor, Notch4
-
Receptors, Cell Surface
-
Receptors, Notch
-
SEL-10 protein, C elegans
-
Ubiquitins
-
Notch4 protein, mouse
-
Ubiquitin-Protein Ligases