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| Subject Categories: Proteins |
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| The EMBO Journal
(2006) 25, 5742–5753, doi:10.1038/sj.emboj.7601450 Published online 30 November 2006 |
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| hRpn13/ADRM1/GP110 is a novel proteasome subunit that binds the deubiquitinating enzyme, UCH37 |
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| Xiao-Bo Qiu1, 2, 4, Song-Ying Ouyang1, 4, Chao-Jun Li3, Shiying Miao1, Linfang Wang1 and Alfred L Goldberg2 |
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1 National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Tsinghua University, Beijing, China 2 Department of Cell Biology, Harvard Medical School, Boston, MA, USA 3 Jiangsu Key Laborotory for Molecular & Medical Biotechnology, Nanjing Normal University, Nanjing, China 4 These authors contributed equally to this work To whom correspondence should be addressed Xiao-Bo Qiu, National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Tsinghua University, 5 Dongdan Santiao, Beijing, China. Tel.: +86 10 6510 5048; Fax: +86 10 6524 0529; E-mail: xbqiu@yahoo.com Alfred L Goldberg, Department of Cell Biology, Harvard Medical School, Boston, MA, USA. Tel.: +1 617 432 1855; Fax: +1 617 232 0173; E-mail: Alfred_Goldberg@hms.harvard.edu Received 5 May 2006; Accepted 24 October 2006; Published online 30 November 2006. |
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| Abstract |
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| The 26S proteasome catalyzes the degradation of most proteins in mammalian cells. To better define its composition and associated regulatory proteins, we developed affinity methods to rapidly purify 26S proteasomes from mammalian cells. By this approach, we discovered a novel 46-kDa (407 residues) subunit of its 19S regulatory complex (previously termed ADRM1 or GP110). As its N-terminal half can be incorporated into the 26S proteasome and is homologous to Rpn13, a 156-residue subunit of the 19S complex in budding yeast, we renamed it human Rpn13 (hRpn13). The C-terminal half of hRpn13 binds directly to the proteasome-associated deubiquitinating enzyme, UCH37, and enhances its isopeptidase activity. Knockdown of hRpn13 in 293T cells increases the cellular levels of ubiquitin conjugates and decreases the degradation of short-lived proteins. Surprisingly, an overproduction of hRpn13 also reduced their degradation. Furthermore, transfection of the C-terminal half of hRpn13 slows proteolysis and induces cell death, probably by acting as a dominant-negative form. Thus in human 26S proteasomes, hRpn13 appears to be important for the binding of UCH37 to the 19S complex and for efficient proteolysis. |
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| Keywords: deubiquitination, hRpn13, proteasome, ubiquitin, UCH37 |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated NEWS AND VIEWS]> Nature Structural & Molecular Biology 13 3 200603 ... Nature Structural & Molecular Biology News and Views (01 Mar 2006) Nature Structural & Molecular Biology News and Views (01 Sep 2004) |
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