Crystal Structure of USP7 Ubiquitin-like Domains with an ICP0 Peptide Reveals a Novel Mechanism Used by Viral and Cellular Proteins to Target USP7
USP7 is a cellular protein that binds and stabilizes many proteins involved in multiple pathways that regulate oncogenesis and as such is recognized as a potential target for cancer therapy. In addition, USP7 is targeted by several viral proteins in order to promote cell survival and viral infection. One such protein is the ICP0 protein of herpes simplex virus 1, which must bind USP7 in order to manipulate the cell in ways that enable efficient viral infection. Here we use a structural approach to define the mechanism of the USP7-ICP0 peptide interaction, revealing a novel binding site on USP7. We then used this information to identify two cellular proteins, GMPS and UHRF1, that also bind USP7 through this binding site. Therefore we have identified a new mechanism by which both viral and cellular proteins can target USP7. This information will be useful for the development of strategies to block specific protein interactions with USP7.
Vyšlo v časopise:
Crystal Structure of USP7 Ubiquitin-like Domains with an ICP0 Peptide Reveals a Novel Mechanism Used by Viral and Cellular Proteins to Target USP7. PLoS Pathog 11(6): e32767. doi:10.1371/journal.ppat.1004950
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.ppat.1004950
Souhrn
USP7 is a cellular protein that binds and stabilizes many proteins involved in multiple pathways that regulate oncogenesis and as such is recognized as a potential target for cancer therapy. In addition, USP7 is targeted by several viral proteins in order to promote cell survival and viral infection. One such protein is the ICP0 protein of herpes simplex virus 1, which must bind USP7 in order to manipulate the cell in ways that enable efficient viral infection. Here we use a structural approach to define the mechanism of the USP7-ICP0 peptide interaction, revealing a novel binding site on USP7. We then used this information to identify two cellular proteins, GMPS and UHRF1, that also bind USP7 through this binding site. Therefore we have identified a new mechanism by which both viral and cellular proteins can target USP7. This information will be useful for the development of strategies to block specific protein interactions with USP7.
Zdroje
1. Du Z, Song J, Wang Y, Zhao Y, Guda K, Yang S, et al. DNMT1 stability is regulated by proteins coordinating deubiquitination and acetylation-driven ubiquitination. Science signaling. 2010;3(146):ra80. doi: 10.1126/scisignal.2001462 21045206
2. Huang Z, Wu Q, Guryanova OA, Cheng L, Shou W, Rich JN, et al. Deubiquitylase HAUSP stabilizes REST and promotes maintenance of neural progenitor cells. Nature cell biology. 2011;13(2):142–52. doi: 10.1038/ncb2153 21258371
3. Li M, Chen D, Shiloh A, Luo J, Nikolaev AY, Qin J, et al. Deubiquitination of p53 by HAUSP is an important pathway for p53 stabilization. Nature. 2002;416(6881):648–53. 11923872
4. Meulmeester E, Maurice MM, Boutell C, Teunisse AF, Ovaa H, Abraham TE, et al. Loss of HAUSP-mediated deubiquitination contributes to DNA damage-induced destabilization of Hdmx and Hdm2. Molecular cell. 2005;18(5):565–76. 15916963
5. Oh YM, Yoo SJ, Seol JH. Deubiquitination of Chfr, a checkpoint protein, by USP7/HAUSP regulates its stability and activity. Biochemical and biophysical research communications. 2007;357(3):615–9. 17442268
6. Schwertman P, Lagarou A, Dekkers DH, Raams A, van der Hoek AC, Laffeber C, et al. UV-sensitive syndrome protein UVSSA recruits USP7 to regulate transcription-coupled repair. Nature genetics. 2012;44(5):598–602. doi: 10.1038/ng.2230 22466611
7. Song MS, Salmena L, Carracedo A, Egia A, Lo-Coco F, Teruya-Feldstein J, et al. The deubiquitinylation and localization of PTEN are regulated by a HAUSP-PML network. Nature. 2008;455(7214):813–7. doi: 10.1038/nature07290 18716620
8. van der Horst A, de Vries-Smits AM, Brenkman AB, van Triest MH, van den Broek N, Colland F, et al. FOXO4 transcriptional activity is regulated by monoubiquitination and USP7/HAUSP. Nature cell biology. 2006;8(10):1064–73. 16964248
9. Saridakis V, Sheng Y, Sarkari F, Holowaty MN, Shire K, Nguyen T, et al. Structure of the p53 binding domain of HAUSP/USP7 bound to Epstein-Barr nuclear antigen 1 implications for EBV-mediated immortalization. Molecular cell. 2005;18(1):25–36. 15808506
10. Sheng Y, Saridakis V, Sarkari F, Duan S, Wu T, Arrowsmith CH, et al. Molecular recognition of p53 and MDM2 by USP7/HAUSP. Nature structural & molecular biology. 2006;13(3):285–91.
11. Sarkari F, Wheaton K, La Delfa A, Mohamed M, Shaikh F, Khatun R, et al. Ubiquitin-specific protease 7 is a regulator of ubiquitin-conjugating enzyme UbE2E1. The Journal of biological chemistry. 2013;288(23):16975–85. doi: 10.1074/jbc.M113.469262 23603909
12. Sarkari F, La Delfa A, Arrowsmith CH, Frappier L, Sheng Y, Saridakis V. Further insight into substrate recognition by USP7: structural and biochemical analysis of the HdmX and Hdm2 interactions with USP7. Journal of molecular biology. 2010;402(5):825–37. doi: 10.1016/j.jmb.2010.08.017 20713061
13. Jagannathan M, Nguyen T, Gallo D, Luthra N, Brown GW, Saridakis V, et al. A role for USP7 in DNA replication. Molecular and cellular biology. 2014;34(1):132–45. doi: 10.1128/MCB.00639-13 24190967
14. Holowaty MN, Sheng Y, Nguyen T, Arrowsmith C, Frappier L. Protein interaction domains of the ubiquitin-specific protease, USP7/HAUSP. The Journal of biological chemistry. 2003;278(48):47753–61. 14506283
15. Faesen AC, Dirac AM, Shanmugham A, Ovaa H, Perrakis A, Sixma TK. Mechanism of USP7/HAUSP activation by its C-terminal ubiquitin-like domain and allosteric regulation by GMP-synthetase. Molecular cell. 2011;44(1):147–59. doi: 10.1016/j.molcel.2011.06.034 21981925
16. Ma H, Chen H, Guo X, Wang Z, Sowa ME, Zheng L, et al. M phase phosphorylation of the epigenetic regulator UHRF1 regulates its physical association with the deubiquitylase USP7 and stability. Proceedings of the National Academy of Sciences of the United States of America. 2012;109(13):4828–33. doi: 10.1073/pnas.1116349109 22411829
17. Sarkari F, Sanchez-Alcaraz T, Wang S, Holowaty MN, Sheng Y, Frappier L. EBNA1-mediated recruitment of a histone H2B deubiquitylating complex to the Epstein-Barr virus latent origin of DNA replication. PLoS pathogens. 2009;5(10):e1000624. doi: 10.1371/journal.ppat.1000624 19834552
18. van der Knaap JA, Kozhevnikova E, Langenberg K, Moshkin YM, Verrijzer CP. Biosynthetic enzyme GMP synthetase cooperates with ubiquitin-specific protease 7 in transcriptional regulation of ecdysteroid target genes. Molecular and cellular biology. 2010;30(3):736–44. doi: 10.1128/MCB.01121-09 19995917
19. van der Knaap JA, Kumar BR, Moshkin YM, Langenberg K, Krijgsveld J, Heck AJ, et al. GMP synthetase stimulates histone H2B deubiquitylation by the epigenetic silencer USP7. Molecular cell. 2005;17(5):695–707. 15749019
20. Reddy BA, van der Knaap JA, Bot AG, Mohd-Sarip A, Dekkers DH, Timmermans MA, et al. Nucleotide biosynthetic enzyme GMP synthase is a TRIM21-controlled relay of p53 stabilization. Molecular cell. 2014;53(3):458–70. doi: 10.1016/j.molcel.2013.12.017 24462112
21. Bronner C. Control of DNMT1 abundance in epigenetic inheritance by acetylation, ubiquitylation, and the histone code. Science signaling. 2011;4(157):pe3. doi: 10.1126/scisignal.2001764 21266713
22. Felle M, Joppien S, Nemeth A, Diermeier S, Thalhammer V, Dobner T, et al. The USP7/Dnmt1 complex stimulates the DNA methylation activity of Dnmt1 and regulates the stability of UHRF1. Nucleic acids research. 2011;39(19):8355–65. doi: 10.1093/nar/gkr528 21745816
23. Qin W, Leonhardt H, Spada F. Usp7 and Uhrf1 control ubiquitination and stability of the maintenance DNA methyltransferase Dnmt1. Journal of cellular biochemistry. 2011;112(2):439–44. doi: 10.1002/jcb.22998 21268065
24. Ma J, Martin JD, Xue Y, Lor LA, Kennedy-Wilson KM, Sinnamon RH, et al. C-terminal region of USP7/HAUSP is critical for deubiquitination activity and contains a second mdm2/p53 binding site. Archives of biochemistry and biophysics. 2010;503(2):207–12. doi: 10.1016/j.abb.2010.08.020 20816748
25. Lee HR, Choi WC, Lee S, Hwang J, Hwang E, Guchhait K, et al. Bilateral inhibition of HAUSP deubiquitinase by a viral interferon regulatory factor protein. Nature structural & molecular biology. 2011;18(12):1336–44.
26. Salsman J, Jagannathan M, Paladino P, Chan PK, Dellaire G, Raught B, et al. Proteomic profiling of the human cytomegalovirus UL35 gene products reveals a role for UL35 in the DNA repair response. Journal of virology. 2012;86(2):806–20. doi: 10.1128/JVI.05442-11 22072767
27. Meredith M, Orr A, Everett R. Herpes simplex virus type 1 immediate-early protein Vmw110 binds strongly and specifically to a 135-kDa cellular protein. Virology. 1994;200(2):457–69. 8178435
28. Sacks WR, Schaffer PA. Deletion mutants in the gene encoding the herpes simplex virus type 1 immediate-early protein ICP0 exhibit impaired growth in cell culture. Journal of virology. 1987;61(3):829–39. 3027408
29. Boutell C, Everett RD. Regulation of alphaherpesvirus infections by the ICP0 family of proteins. The Journal of general virology. 2013;94(Pt 3):465–81. doi: 10.1099/vir.0.048900-0 23239572
30. Lanfranca MP, Mostafa HH, Davido DJ. HSV-1 ICP0: An E3 Ubiquitin Ligase That Counteracts Host Intrinsic and Innate Immunity. Cells. 2014;3(2):438–54. doi: 10.3390/cells3020438 24852129
31. Chelbi-Alix MK, de The H. Herpes virus induced proteasome-dependent degradation of the nuclear bodies-associated PML and Sp100 proteins. Oncogene. 1999;18(4):935–41. 10023669
32. Everett RD, Freemont P, Saitoh H, Dasso M, Orr A, Kathoria M, et al. The disruption of ND10 during herpes simplex virus infection correlates with the Vmw110- and proteasome-dependent loss of several PML isoforms. Journal of virology. 1998;72(8):6581–91. 9658103
33. Lilley CE, Chaurushiya MS, Boutell C, Landry S, Suh J, Panier S, et al. A viral E3 ligase targets RNF8 and RNF168 to control histone ubiquitination and DNA damage responses. The EMBO journal. 2010;29(5):943–55. doi: 10.1038/emboj.2009.400 20075863
34. Lees-Miller SP, Long MC, Kilvert MA, Lam V, Rice SA, Spencer CA. Attenuation of DNA-dependent protein kinase activity and its catalytic subunit by the herpes simplex virus type 1 transactivator ICP0. Journal of virology. 1996;70(11):7471–7. 8892865
35. Canning M, Boutell C, Parkinson J, Everett RD. A RING finger ubiquitin ligase is protected from autocatalyzed ubiquitination and degradation by binding to ubiquitin-specific protease USP7. The Journal of biological chemistry. 2004;279(37):38160–8. 15247261
36. Boutell C, Canning M, Orr A, Everett RD. Reciprocal activities between herpes simplex virus type 1 regulatory protein ICP0, a ubiquitin E3 ligase, and ubiquitin-specific protease USP7. Journal of virology. 2005;79(19):12342–54. 16160161
37. Kalamvoki M, Gu H, Roizman B. Overexpression of the ubiquitin-specific protease 7 resulting from transfection or mutations in the ICP0 binding site accelerates rather than depresses herpes simplex virus 1 gene expression. Journal of virology. 2012;86(23):12871–8. doi: 10.1128/JVI.01981-12 22993145
38. Everett RD, Meredith M, Orr A. The ability of herpes simplex virus type 1 immediate-early protein Vmw110 to bind to a ubiquitin-specific protease contributes to its roles in the activation of gene expression and stimulation of virus replication. Journal of virology. 1999;73(1):417–26. 9847347
39. Everett RD, Boutell C, Orr A. Phenotype of a herpes simplex virus type 1 mutant that fails to express immediate-early regulatory protein ICP0. Journal of virology. 2004;78(4):1763–74. 14747541
40. Daubeuf S, Singh D, Tan Y, Liu H, Federoff HJ, Bowers WJ, et al. HSV ICP0 recruits USP7 to modulate TLR-mediated innate response. Blood. 2009;113(14):3264–75. doi: 10.1182/blood-2008-07-168203 18952891
41. Hu M, Gu L, Li M, Jeffrey PD, Gu W, Shi Y. Structural basis of competitive recognition of p53 and MDM2 by HAUSP/USP7: implications for the regulation of the p53-MDM2 pathway. PLoS biology. 2006;4(2):e27. 16402859
42. Hu M, Li P, Li M, Li W, Yao T, Wu JW, et al. Crystal structure of a UBP-family deubiquitinating enzyme in isolation and in complex with ubiquitin aldehyde. Cell. 2002;111(7):1041–54. 12507430
43. Everett RD, Boutell C, McNair C, Grant L, Orr A. Comparison of the biological and biochemical activities of several members of the alphaherpesvirus ICP0 family of proteins. Journal of virology. 2010;84(7):3476–87. doi: 10.1128/JVI.02544-09 20106921
44. Parkinson J, Everett RD. Alphaherpesvirus proteins related to herpes simplex virus type 1 ICP0 affect cellular structures and proteins. Journal of virology. 2000;74(21):10006–17. 11024129
45. Gelato KA, Tauber M, Ong MS, Winter S, Hiragami-Hamada K, Sindlinger J, et al. Accessibility of different histone H3-binding domains of UHRF1 is allosterically regulated by phosphatidylinositol 5-phosphate. Molecular cell. 2014;54(6):905–19. doi: 10.1016/j.molcel.2014.04.004 24813945
46. Sarkari F, Sheng Y, Frappier L. USP7/HAUSP promotes the sequence-specific DNA binding activity of p53. PloS one. 2010;5(9):e13040. doi: 10.1371/journal.pone.0013040 20885946
47. Sarkari F, Wang X, Nguyen T, Frappier L. The herpesvirus associated ubiquitin specific protease, USP7, is a negative regulator of PML proteins and PML nuclear bodies. PloS one. 2011;6(1):e16598. doi: 10.1371/journal.pone.0016598 21305000
48. Meredith M, Orr A, Elliott M, Everett R. Separation of sequence requirements for HSV-1 Vmw110 multimerisation and interaction with a 135-kDa cellular protein. Virology. 1995;209(1):174–87. 7747467
49. Grochulski P, Fodje MN, Gorin J, Labiuk SL, Berg R. Beamline 08ID-1, the prime beamline of the Canadian Macromolecular Crystallography Facility. Journal of synchrotron radiation. 2011;18(Pt 4):681–4. doi: 10.1107/S0909049511019431 21685687
50. Kabsch W. Processing of X-ray snapshots from crystals in random orientations. Acta crystallographica Section D, Biological crystallography. 2014;70(Pt 8):2204–16. doi: 10.1107/S1399004714013534 25084339
51. Sheldrick GM. Experimental phasing with SHELXC/D/E: combining chain tracing with density modification. Acta crystallographica Section D, Biological crystallography. 2010;66(Pt 4):479–85. doi: 10.1107/S0907444909038360 20383001
52. Murshudov GN, Vagin AA, Dodson EJ. Refinement of macromolecular structures by the maximum-likelihood method. Acta crystallographica Section D, Biological crystallography. 1997;53(Pt 3):240–55. 15299926
53. Otwinowski Z, Minor W. Processing of X-ray diffraction data collected in oscillation mode. Methods in enzymology. 1997;276:307–26.
54. Storoni LC, McCoy AJ, Read RJ. Likelihood-enhanced fast rotation functions. Acta crystallographica Section D, Biological crystallography. 2004;60(Pt 3):432–8. 14993666
55. Emsley P, Cowtan K. Coot: model-building tools for molecular graphics. Acta crystallographica Section D, Biological crystallography. 2004;60(Pt 12 Pt 1):2126–32. 15572765
56. Schrodinger, LLC. The PyMOL Molecular Graphics System, Version 1.3r1. 2010.
Štítky
Hygiena a epidemiológia Infekčné lekárstvo LaboratóriumČlánok vyšiel v časopise
PLOS Pathogens
2015 Číslo 6
- Parazitičtí červi v terapii Crohnovy choroby a dalších zánětlivých autoimunitních onemocnění
- Očkování proti virové hemoragické horečce Ebola experimentální vakcínou rVSVDG-ZEBOV-GP
- Koronavirus hýbe světem: Víte jak se chránit a jak postupovat v případě podezření?
Najčítanejšie v tomto čísle
- HIV Latency Is Established Directly and Early in Both Resting and Activated Primary CD4 T Cells
- A 21st Century Perspective of Poliovirus Replication
- Battling Phages: How Bacteria Defend against Viral Attack
- Adenovirus Tales: From the Cell Surface to the Nuclear Pore Complex