Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2011-3-1
pubmed:abstractText
Fanconi anemia (FA) is a rare cancer-predisposing genetic disease mostly caused by improper regulation of the monoubiquitination of Fanconi anemia complementation group D2 (FANCD2). Genetic studies have indicated that ubiquitin conjugating enzyme UBE2T and HHR6 could regulate FANCD2 monoubiquitination through distinct mechanisms. However, the exact regulation mechanisms of FANCD2 monoubiquitination in response to different DNA damages remain unclear. Here we report that UBE2W, a new ubiquitin conjugating enzyme, could regulate FANCD2 monoubiquitination by mechanisms different from UBE2T or HHR6. Indeed, UBE2W exhibits ubiquitin conjugating enzyme activity and catalyzes the monoubiquitination of PHD domain of Fanconi anemia complementation group L (FANCL) in vitro. UBE2W binds to FANCL, and the PHD domain is both necessary and sufficient for this interaction in mammalian cells. In addition, over-expression of UBE2W in cells promotes the monoubiquitination of FANCD2 and down-regulated UBE2W markedly reduces the UV irradiation-induced but not MMC-induced FANCD2 monoubiquitination. These results indicate that UBE2W regulates FANCD2 monoubiquitination by mechanisms different from UBE2T and HRR6. It may provide an additional regulatory step in the activation of the FA pathway.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0219-1032
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
31
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
113-22
pubmed:meshHeading
pubmed-meshheading:21229326-Amino Acid Sequence, pubmed-meshheading:21229326-Animals, pubmed-meshheading:21229326-Cell Nucleus, pubmed-meshheading:21229326-Fanconi Anemia Complementation Group D2 Protein, pubmed-meshheading:21229326-Fanconi Anemia Complementation Group L Protein, pubmed-meshheading:21229326-HeLa Cells, pubmed-meshheading:21229326-Humans, pubmed-meshheading:21229326-Mice, pubmed-meshheading:21229326-Mitomycin, pubmed-meshheading:21229326-Molecular Sequence Data, pubmed-meshheading:21229326-NIH 3T3 Cells, pubmed-meshheading:21229326-Protein Binding, pubmed-meshheading:21229326-Protein Structure, Tertiary, pubmed-meshheading:21229326-Saccharomyces cerevisiae, pubmed-meshheading:21229326-Ubiquitin-Conjugating Enzymes, pubmed-meshheading:21229326-Ubiquitination, pubmed-meshheading:21229326-Ultraviolet Rays
pubmed:year
2011
pubmed:articleTitle
UBE2W interacts with FANCL and regulates the monoubiquitination of Fanconi anemia protein FANCD2.
pubmed:affiliation
Laboratory of Protein Engineering, Institute of Biotechnology, Beijing, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't