Enzyme to Specifically Cleave Lys48-linked Polyubiquitin
Abstract (Set) A member of the deubiquitinating enzyme (DUB) family has been shown to associate with the ubiquitin E3 ligase GRAIL and to control GRAIL expression. Johns Hopkins researchers now show that the same DUB is a highly specific cleavage enzyme, cleaving only lysine 48 (K48)-linked polyubiquitin chains but not K63-, K29/K6-, or K11-linked polyubiquitin, or linear a-linked polyubiquitin. The high specificity for K48 linkages is not limited to the distal or proximal end of a polyubiquitin chain, and both free and substrate-linked polyubiquitin are disassembled. Description (Set) Proposed Use (Set) The DUB presented here is the first ubiquitin protease identified that is so specific in its cleavage of Lys48 ubiquitin isopeptide bonds. The DUB can be used as a diagnostic tool and laboratory reagent in the specific cleavage and identification of Lys48-linked polyubiquitin and the substrates that are modified by this particular type of polyubiquitin chain.
Wolberger, Cynthia ,Cohen, Robert ,Wang, Tao
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