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PMID: 9389650 Published · ppublish English Journal Article 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.

sel-10, a negative regulator of lin-12 activity in Caenorhabditis elegans, encodes a member of the CDC4 family of proteins.

Genes & development ·Vol. 11 ·No. 23 ·1997-12-01 ·Pages 3182-93

Hubbard EJ, Wu G, Kitajewski J, Greenwald I

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.

MeSH Terms
Amino Acid Sequence Animals Base Sequence Caenorhabditis elegans/genetics,metabolism Caenorhabditis elegans Proteins Cell Cycle Proteins/chemistry,genetics,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,genetics,metabolism Humans Membrane Proteins/genetics,metabolism Mice Molecular Sequence Data Mutation Proto-Oncogene Proteins/genetics,metabolism Receptor, Notch4 Receptors, Cell Surface Receptors, Notch Sequence Homology, Amino Acid Signal Transduction Ubiquitin-Protein Ligases Ubiquitins/metabolism
Chemicals
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
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Hubbard E J
Department of Biochemistry and Molecular Biophysics, Howard Hughes Medical Institute, New York, New York 10032, USA.
Wu G
Kitajewski J
Greenwald I
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
Published
1997-12-01
Pages
3182-93
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC316751
Subset
IM
Grants
NIGMS NIH HHS · GM37602 · United States
Databases
GENBANK
AF020788
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