Min Hu;立川 谷;Muyang Li;Philip D. Jeffrey;Wei Gu;一公 施
Princeton University;China Association for Science and Technology;Columbia College of Physicians and Surgeons
发表时间:2006-2
期 刊:PLoS Biology
语 言:English
U R L: http://www.scopus.com/inward/record.url?scp=33244490784&partnerID=8YFLogxK
Herpesvirus-associated ubiquitin-specific protease (HAUSP, also known as USP7), a deubiquitylating enzyme of the ubiquitin-specific processing protease family, specifically deubiquitylates both p53 and MDM2, hence playing an important yet enigmatic role in the p53-MDM2 pathway. Here we demonstrate that both p53 and MDM2 specifically recognize the N-terminal tumor necrosis factor-receptor associated factor (TRAF)-like domain of HAUSP in a mutually exclusive manner. HAUSP preferentially forms a stable HAUSP-MDM2 complex even in the presence of excess p53. The HAUSP-binding elements were mapped to a peptide fragment in the carboxy-terminus of p53 and to a short-peptide region preceding the acidic domain of MDM2. The crystal structures of the HAUSP TRAF-like domain in complex with p53 and MDM2 peptides, determined at 2.3-Å and 1.7-Å resolutions, respectively, reveal that the MDM2 peptide recognizes the same surface groove in HAUSP as that recognized by p53 but mediates more extensive interactions. Structural comparison led to the identification of a consensus peptide-recognition sequence by HAUSP. These results, together with the structure of a combined substrate-binding-and-deubiquitylation domain of HAUSP, provide important insights into regulation of the p53-MDM2 pathway by HAUSP.
医学与生命科学
农业与生物学
化合物
Scopus度量
年份 | CiteScore | SJR | SNIP |
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1996 | |||
1997 | |||
1998 | |||
1999 | |||
2000 | |||
2001 | |||
2002 | |||
2003 | |||
2004 | 6.047 | 2.24 | |
2005 | 7.087 | 2.498 | |
2006 | 6.415 | 2.45 | |
2007 | 6.899 | 2.801 | |
2008 | 6.663 | 2.852 | |
2009 | 7.722 | 2.949 | |
2010 | 7.847 | 2.734 | |
2011 | 17.3 | 8.744 | 2.601 |
2012 | 17.2 | 8.791 | 2.674 |
2013 | 16.4 | 8.223 | 2.626 |
2014 | 13.6 | 6.814 | 2.314 |
2015 | 11.6 | 5.596 | 2.043 |
2016 | 12 | 5.06 | 1.98 |
2017 | 12.8 | 4.941 | 2.066 |
2018 | 11.3 | 4.783 | 2.102 |
2019 | 10.6 | 4.488 | 2.066 |
2020 | 10 |
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