A HECT domain ubiquitin ligase closely related to the mammalian protein WWP1 is essential for Caenorhabditis elegans embryogenesis.
The highly conserved ubiquitin/proteasome pathway controls the degradation of many critical regulatory proteins. Proteins are posttranslationally conjugated to ubiquitin through a concerted set of reactions involving activating (E1), conjugating (E2), and ligase (E3) enzymes. Ubiquitination targets proteins for proteolysis via the proteasome and may regulate protein function independent of proteolysis. We describe the cloning and functional analysis of new members of the HECT domain family of E3 ubiquitin ligases. Murine Wwp1 encoded a broadly expressed protein containing a C2 domain, four WW domains, and a catalytic HECT domain. A Caenorhabditis elegans gene was cloned encoding a HECT domain protein (CeWWP1), which was highly homologous to murine and human WWP1. Disruption of CeWwp1 via RNA interference yielded an embryonic lethal phenotype, despite the presence of at least six additional C. elegans genes encoding HECT domain proteins. The embryonic lethality was characterized by grossly abnormal morphogenesis during late embryogenesis, despite normal proliferation early in embryogenesis. CeWWP1 must therefore have unique and nonredundant functions critical for embryogenesis.
Huang
K
K
University of Wisconsin Medical School, Department of Pharmacology, Molecular and Cellular Pharmacology Program, 387 Medical Science Center, 1300 University Avenue, 53706, Madison, WI, USA.
Johnson
K D
KD
Petcherski
A G
AG
Vandergon
T
T
Mosser
E A
EA
Copeland
N G
NG
Jenkins
N A
NA
Kimble
J
J
Bresnick
E H
EH
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D017173:Caenorhabditis elegans / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins; D002455:Cell Division; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D004625:Embryo, Nonmammalian / Q000378:metabolism; D047108:Embryonic Development; D019143:Evolution, Molecular; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D008025:Ligases / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009115:Muridae; D010802:Phylogeny; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D044767:Ubiquitin-Protein Ligases
D029742:Caenorhabditis elegans Proteins; D018076:DNA, Complementary; C413402:wwp-1 protein, C elegans; D044767:Ubiquitin-Protein Ligases; D008025:Ligases