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General Comment |
In eukaryotic cells, the covalent attachment of ubiquitin (191320) to proteins plays a role in a variety of cellular processes. In many cases, ubiquitination leads to protein degradation by the 26S proteasome. Protein ubiquitination is reversible, and the removal of ubiquitin is catalyzed by deubiquitinating enzymes, or DUBs. Members of one DUB subfamily, the ubiquitin-specific proteases, or UBPs (EC 3.1.2.15 ), have been identified in a variety of organisms. UBPs are specialized thiol proteases that cleave ubiquitin from several types of substrates.
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Comment |
Baek KH, et al reported that DUB-1A, encoding the shortest form amongst DUB subfamily members of deubiquitinating enzymes so far, has been identified . The sequence analysis showed that DUB-1A encodes a 468 amino acid with a molecular weight of approximately 51 kDa containing a putative catalytic domain (Cys, His, and Asp) conserved among DUB proteins. The amino acid sequence of DUB-1A showed a homology of 84.5%, 84.7%, and 85.3% identity to that of DUB-1, DUB-2, and DUB-2A, respectively. RT-PCR reaction analysis revealed that DUB-1A is expressed not only in B-lymphocytes in response to IL-3 stimulation, but also in T-lymphocytes, brain, heart, liver, lung, kidney, ovary, and spleen. This suggests that DUB-1A may play essential roles in each of these organs. In vivo and in vitro deubiquitinating enzyme assays showed that DUB-1A has functional deubiquitinating activity and the 5 flanking sequence of DUB-1A has a functional enhancer domain as shown in DUB-1 and DUB-2A. Interestingly, immunoblotting analysis revealed that DUB-1A is polyubiquitinated, indicating that it is degraded through the proteasome-mediated degradation. In the absence of JAK2, DUB-1A was less expressed. This suggests that DUB-1A functions downstream of JAK2 kinase in IL-3 signaling pathway.
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