The enzymes of the ubiquitylation pathway play a pivotal role in a number of cellular processes including the 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). UBE2D3 is a member of the E2 ubiquitin-conjugating enzyme family and cloning of the gene was first described by Jensen et al. (1995). Human UBE2D3 shares 94% and 79% sequence identity with the Drosophila and S. cerevisiae homologues respectively. UBE2D3 can conjugate ubiquitin to targets such as p53 in an E6AP dependent manner (Jensen et al., 1995). Upregulation of UBE2D3 following treatment with Retinoic Acid (RA) has been shown to induce differentiation and growth arrest in NB4 human promyelocytic cells. UBE2D3 associates with Cyclin D1 and mediates retinoic acid induced cyclin D1 degradation (Hattori et al., 2007). Activation of the IKK complex is mediated by unanchored polyubiquitin chains formed by UBE2D3 and TRAF6 (Xia et al., 2009). Zipper-interacting protein kinase (ZIPK) is a serine/threonine kinase implicated in cell death and transcriptional regulation. UBE2D3 induces ZIPK accumulation in promyelocytic leukemia protein nuclear bodies resulting in their ubiquitylation (Ohbayashi et al., 2008). Meibomian cell carcinoma (MCC) is a malignant tumour of the meibomian glands located in the eyelids, UBE2D3 has been identified by RT/PCR as one of five genes found to be upregulated in MCC tumours (Kumar et al., 2007).
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