RRC ID 4330
Author Killian DJ, Harvey E, Johnson P, Otori M, Mitani S, Xue D.
Title SKR-1, a homolog of Skp1 and a member of the SCF(SEL-10) complex, regulates sex-determination and LIN-12/Notch signaling in C. elegans.
Journal Dev. Biol.
Abstract Sex-determination in Caenorhabditis elegans requires regulation of gene transcription and protein activity and stability. sel-10 encodes a WD40-repeat-containing F-box protein that likely mediates the ubiquitin-mediated degradation of important sex-determination factors. Loss of sel-10 results in a mild masculinization of hermaphrodites, whereas dominant alleles of sel-10, such as sel-10(n1074), cause a more severe masculinization, including a reversal of the life versus death decision in sex-specific neurons. To investigate about how sel-10 regulates sex-determination, we conducted a sel-10(n1074) suppressor screen and isolated a weak loss-of-function allele of skr-1, one of 21 Skp1-related genes in C. elegans. Skp1, Cullin, and F-box proteins, such as SEL-10, are components of the SCF E3 ubiquitin-ligase complex. We present genetic evidence that the sel-10(n1074) masculinization phenotype is dependent upon skr-1 and cul-1 activity. Furthermore, we show that the SKR-1(M140I) weak loss-of-function mutation interferes with SKR-1/SEL-10 binding. Unexpectedly, we found that the G567E substitution in SEL-10 caused by the n1074 allele impairs the binding of SEL-10 to SKR-1 and the dimerization of SEL-10, which may be important for SEL-10 function. Our results suggest that SKR-1, CUL-1 and SEL-10 constitute an SCF E3 ligase complex that plays an important role in modulating sex-determination and LIN-12/Notch signaling in C. elegans.
Volume 322(2)
Pages 322-31
Published 2008-10-15
DOI 10.1016/j.ydbio.2008.07.035
PII S0012-1606(08)01101-9
PMID 18718460
PMC PMC2626169
MeSH Amino Acid Sequence Animals Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cell Cycle Proteins / genetics Cell Cycle Proteins / metabolism* Cullin Proteins / metabolism Dimerization Membrane Proteins Molecular Sequence Data Mutation, Missense Neurons / physiology Nuclear Proteins / genetics Nuclear Proteins / metabolism* Receptors, Notch / metabolism* SKP Cullin F-Box Protein Ligases / genetics SKP Cullin F-Box Protein Ligases / metabolism* Sex Determination Processes* Signal Transduction Ubiquitin-Protein Ligase Complexes
IF 2.936
Times Cited 9
C.elegans tm2391