Abstract |
USP28 ( ubiquitin-specific protease 28) is a deubiquitinating enzyme that has been implicated in the DNA damage response, the regulation of Myc signaling, and cancer progression. The half-life stability of major regulators of critical cellular pathways depends on the activities of specific ubiquitin E3 ligases that target them for proteosomal degradation and deubiquitinating enzymes that promote their stabilization. One function of the post-translational small ubiquitin modifier (SUMO) is the regulation of enzymatic activity of protein targets. In this work, we demonstrate that the SUMO modification of the N-terminal domain of USP28 negatively regulates its deubiquitinating activity, revealing a role for the N-terminal region as a regulatory module in the control of USP28 activity. Despite the presence of ubiquitin-binding domains in the N-terminal domain, its truncation does not impair deubiquitinating activity on diubiquitin or polyubiquitin chain substrates. In contrast to other characterized USP deubiquitinases, our results indicate that USP28 has a chain preference activity for Lys(11), Lys(48), and Lys(63) diubiquitin linkages.
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Authors | Yang Zhen, Philip A Knobel, Travis H Stracker, David Reverter |
Journal | The Journal of biological chemistry
(J Biol Chem)
Vol. 289
Issue 50
Pg. 34838-50
(Dec 12 2014)
ISSN: 1083-351X [Electronic] United States |
PMID | 25359778
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2014 by The American Society for Biochemistry and Molecular Biology, Inc. |
Chemical References |
- SUMO-1 Protein
- USP28 protein, human
- Ubiquitin Thiolesterase
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Topics |
- Amino Acid Sequence
- Catalytic Domain
- Humans
- Models, Molecular
- Molecular Sequence Data
- Protein Processing, Post-Translational
- SUMO-1 Protein
(metabolism)
- Substrate Specificity
- Sumoylation
- Ubiquitin Thiolesterase
(chemistry, metabolism)
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