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2muu

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Revision as of 12:22, 16 November 2017

The Proteolytic Activity of Ubiquitin-specific Protease 28 Is Modulated by the N-terminal Domain

Structural highlights

2muu is a 1 chain structure with sequence from Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	USP28, KIAA1515 (HUMAN)
Activity:	Ubiquitinyl hydrolase 1, with EC number 3.4.19.12
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[UBP28_HUMAN] Deubiquitinase involved in DNA damage response checkpoint and MYC proto-oncogene stability. Involved in DNA damage induced apoptosis by specifically deubiquitinating proteins of the DNA damage pathway such as CLSPN. Also involved in G2 DNA damage checkpoint, by deubiquitinating CLSPN, and preventing its degradation by the anaphase promoting complex/cyclosome (APC/C). In contrast, it does not deubiquitinate PLK1. Specifically deubiquitinates MYC in the nucleoplasm, leading to prevent MYC degradation by the proteasome: acts by specifically interacting with isoform 1 of FBXW7 (FBW7alpha) in the nucleoplasm and counteracting ubiquitination of MYC by the SCF(FBW7) complex. In contrast, it does not interact with isoform 4 of FBXW7 (FBW7gamma) in the nucleolus, allowing MYC degradation and explaining the selective MYC degradation in the nucleolus.^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

The deubiquitinase ubiquitin-specific protease 28 (Usp28) contains a ubiquitin-binding region (UBR) composed of one ubiquitin-associated domain (UBA) and one ubiquitin-interacting motif (UIM) at its N-terminus. It is of interest that an additional small ubiquitin-like modifier (SUMO)-interacting motif (SIM) is located next to its UIM. To date, the functional role of the Usp28 UBR is still not understood. To elucidate the regulatory mechanism of the UBR on the full functional display of Usp28, in the present study, NMR and biochemical approaches were applied. The solution structure of Usp28 UBR was obtained, and the key residues responsible for ubiquitin and SUMO1/2 recognition were identified. In addition, we find that the ubiquitin-binding ability of Usp28 UBR was required for full enzymatic activity of Usp28, whereas binding of SUMO1/2 impaired the catalytic activity of the enzyme by competitively blocking its interactions with ubiquitin substrates. Our findings provide a first insight into understanding how the enzymatic activity of Usp28 is regulated by its non-catalytic UBR and endogenous ligands.

The N-terminal ubiquitin-binding region of ubiquitin-specific protease 28 modulates its deubiquitination function: NMR structural and mechanistic insights.,Wen Y, Shi L, Ding Y, Cui R, He WT, Hu HY, Zhang N Biochem J. 2015 Oct 15;471(2):155-65. doi: 10.1042/BJ20150088. Epub 2015 Aug 12. PMID:26268556^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Zhang D, Zaugg K, Mak TW, Elledge SJ. A role for the deubiquitinating enzyme USP28 in control of the DNA-damage response. Cell. 2006 Aug 11;126(3):529-42. PMID:16901786 doi:http://dx.doi.org/10.1016/j.cell.2006.06.039
↑ Popov N, Wanzel M, Madiredjo M, Zhang D, Beijersbergen R, Bernards R, Moll R, Elledge SJ, Eilers M. The ubiquitin-specific protease USP28 is required for MYC stability. Nat Cell Biol. 2007 Jul;9(7):765-74. Epub 2007 Jun 10. PMID:17558397 doi:http://dx.doi.org/10.1038/ncb1601
↑ Popov N, Herold S, Llamazares M, Schulein C, Eilers M. Fbw7 and Usp28 regulate myc protein stability in response to DNA damage. Cell Cycle. 2007 Oct 1;6(19):2327-31. Epub 2007 Jul 26. PMID:17873522
↑ Bassermann F, Frescas D, Guardavaccaro D, Busino L, Peschiaroli A, Pagano M. The Cdc14B-Cdh1-Plk1 axis controls the G2 DNA-damage-response checkpoint. Cell. 2008 Jul 25;134(2):256-67. doi: 10.1016/j.cell.2008.05.043. PMID:18662541 doi:http://dx.doi.org/10.1016/j.cell.2008.05.043
↑ Wen Y, Shi L, Ding Y, Cui R, He WT, Hu HY, Zhang N. The N-terminal ubiquitin-binding region of ubiquitin-specific protease 28 modulates its deubiquitination function: NMR structural and mechanistic insights. Biochem J. 2015 Oct 15;471(2):155-65. doi: 10.1042/BJ20150088. Epub 2015 Aug 12. PMID:26268556 doi:http://dx.doi.org/10.1042/BJ20150088

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2muu"

@@ Line 3: / Line 3: @@
 <StructureSection load='2muu' size='340' side='right' caption='[[2muu]], [[NMR_Ensembles_of_Models | 14 NMR models]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2muu]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MUU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2MUU FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2muu]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MUU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2MUU FirstGlance]. <br>
-</td></tr><tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ubiquitinyl_hydrolase_1 Ubiquitinyl hydrolase 1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.19.12 3.4.19.12] </span></td></tr>
+</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">USP28, KIAA1515 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2muu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2muu OCA], [http://pdbe.org/2muu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2muu RCSB], [http://www.ebi.ac.uk/pdbsum/2muu PDBsum]</span></td></tr>
+<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ubiquitinyl_hydrolase_1 Ubiquitinyl hydrolase 1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.19.12 3.4.19.12] </span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2muu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2muu OCA], [http://pdbe.org/2muu PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2muu RCSB], [http://www.ebi.ac.uk/pdbsum/2muu PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2muu ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 22: / Line 23: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Ubiquitinyl hydrolase 1]]
 [[Category: Shi, L]]

2muu

From Proteopedia

Revision as of 12:22, 16 November 2017

The Proteolytic Activity of Ubiquitin-specific Protease 28 Is Modulated by the N-terminal Domain

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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