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

Kai Huang; Kirby D. Johnson; Andrei G. Petcherski; Thomas Vandergon; Eric A. Mosser; Neal G. Copeland; Nancy A. Jenkins; Judith Kimble; Emery H. Bresnick

doi:10.1016/S0378-1119(00)00216-X

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

Kai Huang, Kirby D. Johnson, Andrei G. Petcherski, Thomas Vandergon, Eric A. Mosser, Neal G. Copeland, Nancy A. Jenkins, Judith Kimble, Emery H. Bresnick^*

^*Corresponding author for this work

Program in Biological Sciences

Research output: Contribution to journal › Article › peer-review

33 Scopus citations

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.

Original language	English (US)
Pages (from-to)	137-145
Number of pages	9
Journal	Gene
Volume	252
Issue number	1-2
DOIs	https://doi.org/10.1016/S0378-1119(00)00216-X
State	Published - Jul 11 2000

Funding

The authors acknowledge support from the Milwaukee Foundation (EHB), the Leukemia Society of America (EHB), and the National Institutes of Health (DK55700) (EHB) and by the National Cancer Institute, DHHS (NGC and NAJ). Emery H. Bresnick is a Scholar of the Leukemia and Lymphoma Society, and a Shaw Scientist. Judith Kimble is an Investigator with the HHMI. Andrei Petcherski was supported by an HHMI predoctoral fellowship. We thank Greg Pirozzi for the human Wwp1 plasmid. We thank Debra J. Gilbert for excellent technical assistance.

Keywords

Gene family
Morphogenesis
Ubiquitination
WW domain

ASJC Scopus subject areas

Genetics

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10.1016/S0378-1119(00)00216-X

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@article{41c0aab8069b42e6abb9325863f07184,

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

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.",

keywords = "Gene family, Morphogenesis, Ubiquitination, WW domain",

author = "Kai Huang and Johnson, {Kirby D.} and Petcherski, {Andrei G.} and Thomas Vandergon and Mosser, {Eric A.} and Copeland, {Neal G.} and Jenkins, {Nancy A.} and Judith Kimble and Bresnick, {Emery H.}",

note = "Funding Information: The authors acknowledge support from the Milwaukee Foundation (EHB), the Leukemia Society of America (EHB), and the National Institutes of Health (DK55700) (EHB) and by the National Cancer Institute, DHHS (NGC and NAJ). Emery H. Bresnick is a Scholar of the Leukemia and Lymphoma Society, and a Shaw Scientist. Judith Kimble is an Investigator with the HHMI. Andrei Petcherski was supported by an HHMI predoctoral fellowship. We thank Greg Pirozzi for the human Wwp1 plasmid. We thank Debra J. Gilbert for excellent technical assistance. Copyright: Copyright 2007 Elsevier B.V., All rights reserved.",

year = "2000",

month = jul,

day = "11",

doi = "10.1016/S0378-1119(00)00216-X",

language = "English (US)",

volume = "252",

pages = "137--145",

journal = "Gene",

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T1 - A HECT domain ubiquitin ligase closely related to the mammalian protein WWP1 is essential for Caenorhabditis elegans embryogenesis

AU - Huang, Kai

AU - Johnson, Kirby D.

AU - Petcherski, Andrei G.

AU - Vandergon, Thomas

AU - Mosser, Eric A.

AU - Copeland, Neal G.

AU - Jenkins, Nancy A.

AU - Kimble, Judith

AU - Bresnick, Emery H.

N1 - Funding Information: The authors acknowledge support from the Milwaukee Foundation (EHB), the Leukemia Society of America (EHB), and the National Institutes of Health (DK55700) (EHB) and by the National Cancer Institute, DHHS (NGC and NAJ). Emery H. Bresnick is a Scholar of the Leukemia and Lymphoma Society, and a Shaw Scientist. Judith Kimble is an Investigator with the HHMI. Andrei Petcherski was supported by an HHMI predoctoral fellowship. We thank Greg Pirozzi for the human Wwp1 plasmid. We thank Debra J. Gilbert for excellent technical assistance. Copyright: Copyright 2007 Elsevier B.V., All rights reserved.

PY - 2000/7/11

Y1 - 2000/7/11

N2 - 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.

AB - 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.

KW - Gene family

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KW - Ubiquitination

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ER -

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

Abstract

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Keywords

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