The enzymes of the ubiquitylation pathway play a pivotal role in a number of cellular processes including regulated and targeted proteasomal degradation of substrate proteins. Three classes of enzymes are involved in the process of ubiquitylation; activating enzymes (E1s), conjugating enzymes (E2s) and protein ligases (E3s). UBE2T is a member of the E2 conjugating enzyme family and cloning of the human gene was first described by Zhang et al. (2000). UBE2T is integral to the Fanconi Anemia pathway for DNA damage repair. UBE2T binds to the C-terminal PH domain of FANCL the ubiquitin ligase subunit of the Fanconi Anemia (FA) core complex, which leads to the monoubiquitylation of FANCD2 and FANCI (Longerich et al., 2009; Machida et al., 2006). E3 ligase activity is not determined by assembly of the FA core complex but by the DNA damage-induced subcellular localization of the complex to chromatin. UBE2T and FANCD2 access this subcellular fraction independently and FANCD2 monoubiquitylation is regulated by the formation of an E2/E3 holoenzyme on chromatin. DNA damage in UBE2T-depleted human osteosarcoma cells leads to the formation of abnormal chromosomes that are a hallmark of FA (Alpi et al., 2007). UBE2T expression has been analysed in lung cancer tissue and compared to normal human tissue. UBE2T was found to be significantly upregulated at both the protein and mRNA level suggesting involvement in the malignant cell phenotype (Hao et al., 2008).
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