https://www.ncbi.nlm.nih.gov/pubmed/16005295
Curr Biol. 2005 Jul 12;15(13):1217-21.
The zinc finger of the CSN-associated deubiquitinating enzyme USP15 is essential to rescue the E3 ligase Rbx1.
Hetfeld BK1, Helfrich A, Kapelari B, Scheel H, Hofmann K, Guterman A, Glickman M, Schade R, Kloetzel PM, Dubiel W. Abstract
The
COP9 signalosome (CSN) is a conserved protein complex found in all
eukaryotic cells and involved in the regulation of the ubiquitin
(Ub)/26S proteasome system. It binds numerous proteins, including the Ub
E3 ligases and the deubiquitinating
enzyme Ubp12p, the S. pombe ortholog of human USP15. We found that
USP15 copurified with the human CSN complex. Isolated CSN complex
exhibited protease activity that deubiquitinated poly-Ub substrates and
was completely inhibited by o-phenanthroline (OPT), a metal-chelating
agent. Surprisingly, the recombinant USP15 was also not able to cleave
isopeptide bonds of poly-Ub chains in presence of OPT. Detailed analysis
of USP sequences led to the discovery of a novel zinc (Zn) finger in
USP15 and related USPs. Mutation of a single conserved cysteine residue
in the predicted Zn binding motif resulted in the loss of USP15
capability to degrade poly-Ub substrates, indicating that the Zn finger
is essential for the cleavage of poly-Ub chains. Moreover, pulldown
experiments demonstrated diminished binding of tetra-Ub to mutated
USP15. Cotransfection of USP15 and the Ub ligase Rbx1 revealed that the
wild-type deubiquitinating enzyme, but not the USP15 mutant with a defective Zn finger, stabilized Rbx1 toward the Ub system, most likely by reversing poly/autoubiquitination. In summary, a functional Zn finger
of USP15 is needed to maintain a conformation essential for
disassembling poly-Ub chains, a prerequisite for rescuing the E3 ligase
Rbx1.
Geeni USP ( 12q14.1) Also known asUNPH4; UNPH-2
- Summary This gene encodes a member of the ubiquitin specific protease (USP) family of deubiquitinating enzymes. USP enzymes play critical roles in ubiquitin-dependent processes through polyubiquitin chain disassembly and hydrolysis of ubiquitin-substrate bonds. The encoded protein associates with the COP9 signalosome, and also plays a role in transforming growth factor beta signalling through deubiquitination of receptor-activated SMAD transcription factors. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 2. [provided by RefSeq, Nov 2011]
- Expression Ubiquitous expression in bone marrow (RPKM 16.1), appendix (RPKM 8.0) and 24 other
- Preferred Names ubiquitin carboxyl-terminal hydrolase 15
- Names
- deubiquitinating enzyme 15
- ubiquitin thioesterase 15
- ubiquitin thiolesterase 15
- ubiquitin-specific-processing protease 15
- https://www.ncbi.nlm.nih.gov/protein/NP_001239007.1
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