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A HECT domain ubiquitin ligase closely related to the mammalian protein WWP1 is essential for Caenorhabditis elegans embryogenesis

  1. Author:
    Huang, K.
    Johnson, K. D.
    Petcherski, A. G.
    Vandergon, T.
    Mosser, E. A.
    Copeland, N. G.
    Jenkins, N. A.
    Kimble, J.
    Bresnick, E. H.

  2. Author Address

    Bresnick EH Univ Wisconsin, Sch Med, Dept Pharmacol, Mol & Cellular Pharmacol Program 387 Med Sci Ctr,1300 Univ Ave Madison, WI 53706 USA Univ Wisconsin, Sch Med, Dept Pharmacol, Mol & Cellular Pharmacol Program Madison, WI 53706 USA Univ Wisconsin, Howard Hughes Med Inst Madison, WI 53706 USA Univ Wisconsin, Dept Biochem Madison, WI 53706 USA Pepperdine Univ, Div Nat Sci Malibu, CA 90263 USA NCI, Mammalian Genet Lab, Frederick Canc Res & Dev Ctr Frederick, MD 21702 USA
    1. Year: 2000
  2. Journal: Gene
    1. 252
    2. 1-2
    3. Pages: 137-145
  4. Type of Article: Article
  1. Abstract:

    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. (C) 2000 Elsevier Science B.V. All rights reserved. [References: 33]

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