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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2002-1-28
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pubmed:databankReference |
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pubmed:abstractText |
Ubiquitin ligases define the substrate specificity of protein ubiquitination and subsequent proteosomal degradation. The catalytic sequence was first characterized in the C terminus of E6-associated protein (E6AP) and referred to as the HECT (homologous to E6AP C terminus) domain. The human homologue of the regulator of cell proliferation hyperplastic discs in Drosophila, designated hHYD, is a HECT-domain ubiquitin ligase. Here we show that hHYD provides a ubiquitin system for a cellular response to DNA damage. A yeast two-hybrid screen showed that DNA topoisomerase IIbeta-binding protein 1 (TopBP1) interacted with hHYD. Endogenous hHYD bound the BRCA1 C-terminus domains of TopBP1 that are highlighted in DNA damage checkpoint proteins and cell cycle regulators. Using an in vitro reconstitution, specific E2 (ubiquitin-conjugating) enzymes (human UbcH4, UbcH5B, and UbcH5C) transferred ubiquitin molecules to hHYD, leading to the ubiquitination of TopBP1. TopBP1 was usually ubiquitinated and degraded by the proteosome, whereas X-irradiation diminished the ubiquitination of TopBP1 probably via the phosphorylation, resulting in the stable colocalization of up-regulated TopBP1 with gamma-H2AX nuclear foci in DNA breaks. These results demonstrated that hHYD coordinated TopBP1 in the DNA damage response.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Dithiothreitol,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Synthases,
http://linkedlifedata.com/resource/pubmed/chemical/TOPBP1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/UBR5 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin-Protein Ligases
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
277
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3599-605
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:11714696-Animals,
pubmed-meshheading:11714696-COS Cells,
pubmed-meshheading:11714696-Carrier Proteins,
pubmed-meshheading:11714696-Catalytic Domain,
pubmed-meshheading:11714696-Cercopithecus aethiops,
pubmed-meshheading:11714696-DNA Damage,
pubmed-meshheading:11714696-DNA-Binding Proteins,
pubmed-meshheading:11714696-Dithiothreitol,
pubmed-meshheading:11714696-Gene Library,
pubmed-meshheading:11714696-HeLa Cells,
pubmed-meshheading:11714696-Humans,
pubmed-meshheading:11714696-Molecular Sequence Data,
pubmed-meshheading:11714696-Muscle, Skeletal,
pubmed-meshheading:11714696-Nuclear Proteins,
pubmed-meshheading:11714696-Peptide Synthases,
pubmed-meshheading:11714696-Phosphorylation,
pubmed-meshheading:11714696-Saccharomyces cerevisiae,
pubmed-meshheading:11714696-Signal Transduction,
pubmed-meshheading:11714696-Substrate Specificity,
pubmed-meshheading:11714696-Transfection,
pubmed-meshheading:11714696-Ubiquitin,
pubmed-meshheading:11714696-Ubiquitin-Protein Ligases,
pubmed-meshheading:11714696-X-Rays
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pubmed:year |
2002
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pubmed:articleTitle |
Cooperation of HECT-domain ubiquitin ligase hHYD and DNA topoisomerase II-binding protein for DNA damage response.
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pubmed:affiliation |
Department of Tumor Genetics and Biology and Department of Internal Medicine I, Kumamoto University School of Medicine, 2-2-1 Honjo, Kumamoto 860-0811, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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