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| {{STRUCTURE_2f1w| PDB=2f1w | SCENE= }} | | {{STRUCTURE_2f1w| PDB=2f1w | SCENE= }} |
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| '''Crystal structure of the TRAF-like domain of HAUSP/USP7'''
| | ===Crystal structure of the TRAF-like domain of HAUSP/USP7=== |
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| ==Overview==
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| 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-A and 1.7-A 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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_16402859}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 16402859 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_16402859}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Ubp]] | | [[Category: Ubp]] |
| [[Category: Usp7]] | | [[Category: Usp7]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 03:21:52 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 13:41:58 2008'' |