دورية أكاديمية
أعرض في EDS

Ubiquilin-2 differentially regulates polyglutamine disease proteins.

التفاصيل البيبلوغرافية
العنوان: Ubiquilin-2 differentially regulates polyglutamine disease proteins.
المؤلفون: Gerson JE; Department of Neurology, University of Michigan, Ann Arbor, MI 48109-2200, USA., Safren N; Department of Neurology, University of Michigan, Ann Arbor, MI 48109-2200, USA., Fischer S; Department of Neurology, University of Michigan, Ann Arbor, MI 48109-2200, USA., Patel R; Department of Neurology, University of Michigan, Ann Arbor, MI 48109-2200, USA., Crowley EV; Department of Neurology, University of Michigan, Ann Arbor, MI 48109-2200, USA., Welday JP; Department of Neurology, University of Michigan, Ann Arbor, MI 48109-2200, USA., Windle AK; Department of Neurology, University of Michigan, Ann Arbor, MI 48109-2200, USA., Barmada S; Department of Neurology, University of Michigan, Ann Arbor, MI 48109-2200, USA., Paulson HL; Department of Neurology, University of Michigan, Ann Arbor, MI 48109-2200, USA., Sharkey LM; Department of Neurology, University of Michigan, Ann Arbor, MI 48109-2200, USA.
المصدر: Human molecular genetics [Hum Mol Genet] 2020 Aug 29; Vol. 29 (15), pp. 2596-2610.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: IRL Press at Oxford University Press Country of Publication: England NLM ID: 9208958 Publication Model: Print Cited Medium: Internet ISSN: 1460-2083 (Electronic) Linking ISSN: 09646906 NLM ISO Abbreviation: Hum Mol Genet Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Oxford, England ; New York : IRL Press at Oxford University Press, c1992-
مواضيع طبية MeSH: Ataxin-3/*genetics , Huntingtin Protein/*genetics , Huntington Disease/*genetics , Machado-Joseph Disease/*genetics, Adaptor Proteins, Signal Transducing/genetics ; Animals ; Autophagy-Related Proteins/genetics ; Disease Models, Animal ; Exons ; Genetic Heterogeneity ; Humans ; Mice ; Neurons/metabolism ; Neurons/pathology ; Peptides/genetics ; Proteasome Endopeptidase Complex
مستخلص: Divergent protein context helps explain why polyglutamine expansion diseases differ clinically and pathologically. This heterogeneity may also extend to how polyglutamine disease proteins are handled by cellular pathways of proteostasis. Studies suggest, for example, that the ubiquitin-proteasome shuttle protein Ubiquilin-2 (UBQLN2) selectively interacts with specific polyglutamine disease proteins. Here we employ cellular models, primary neurons and mouse models to investigate the potential differential regulation by UBQLN2 of two polyglutamine disease proteins, huntingtin (HTT) and ataxin-3 (ATXN3). In cells, overexpressed UBQLN2 selectively lowered levels of full-length pathogenic HTT but not of HTT exon 1 fragment or full-length ATXN3. Consistent with these results, UBQLN2 specifically reduced accumulation of aggregated mutant HTT but not mutant ATXN3 in mouse models of Huntington's disease (HD) and spinocerebellar ataxia type 3 (SCA3), respectively. Normally a cytoplasmic protein, UBQLN2 translocated to the nuclei of neurons in HD mice but not in SCA3 mice. Remarkably, instead of reducing the accumulation of nuclear mutant ATXN3, UBQLN2 induced an accumulation of cytoplasmic ATXN3 aggregates in neurons of SCA3 mice. Together these results reveal a selective action of UBQLN2 toward polyglutamine disease proteins, indicating that polyglutamine expansion alone is insufficient to promote UBQLN2-mediated clearance of this class of disease proteins. Additional factors, including nuclear translocation of UBQLN2, may facilitate its action to clear intranuclear, aggregated disease proteins like HTT.
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References: Nat Cell Biol. 2002 Sep;4(9):725-30. (PMID: 12198498)
Neurobiol Aging. 2012 Oct;33(10):2527.e3-10. (PMID: 22717235)
J Biol Chem. 2010 Dec 10;285(50):39303-13. (PMID: 20943656)
J Vis Exp. 2019 Jan 19;(143):. (PMID: 30735193)
Nat Commun. 2014 Aug 21;5:4638. (PMID: 25144244)
Ann Neurol. 2014 May;75(5):793-798. (PMID: 24771548)
J Biol Chem. 2008 Jul 4;283(27):18538-44. (PMID: 18467327)
Mol Cell Proteomics. 2019 Sep;18(9):1705-1720. (PMID: 31138642)
Acta Neuropathol. 2012 Jul;124(1):149-51. (PMID: 22661321)
Neurobiol Dis. 2015 Oct;82:281-288. (PMID: 26141599)
Proc Natl Acad Sci U S A. 2005 Mar 8;102(10):3840-5. (PMID: 15738408)
Nature. 2018 Nov;563(7731):407-411. (PMID: 30429547)
Nature. 2011 Aug 21;477(7363):211-5. (PMID: 21857683)
Exp Cell Res. 2007 Feb 1;313(3):538-50. (PMID: 17141218)
Proc Natl Acad Sci U S A. 2001 Oct 23;98(22):12784-9. (PMID: 11675509)
Hum Mol Genet. 2002 May 1;11(9):1075-94. (PMID: 11978767)
PLoS One. 2015 Jun 15;10(6):e0130162. (PMID: 26075709)
Mol Cell. 2018 Mar 15;69(6):965-978.e6. (PMID: 29526694)
J Biol Chem. 2010 Mar 19;285(12):8808-23. (PMID: 20086007)
Dis Model Mech. 2018 Jan 30;11(1):. (PMID: 29419417)
J Cell Biol. 2009 Oct 19;187(2):201-17. (PMID: 19822669)
J Biol Chem. 2004 Oct 1;279(40):42290-301. (PMID: 15280365)
EMBO J. 1998 Nov 2;17(21):6144-54. (PMID: 9799224)
J Neurochem. 2014 Apr;129(1):99-106. (PMID: 24215460)
Elife. 2018 Jul 17;7:. (PMID: 30015619)
J Biol Chem. 2002 Apr 5;277(14):11691-5. (PMID: 11805121)
Genetics. 2014 May;197(1):193-7. (PMID: 24621829)
Mol Cell. 2000 Aug;6(2):409-19. (PMID: 10983987)
Hum Mol Genet. 2006 Aug 15;15(16):2409-20. (PMID: 16822850)
J Neurosci. 2011 Sep 7;31(36):13002-14. (PMID: 21900579)
Brain Res. 2013 Aug 2;1524:62-73. (PMID: 23774650)
Biochem Biophys Res Commun. 2016 Apr 1;472(2):324-31. (PMID: 26944018)
J Neurosci. 2010 Aug 4;30(31):10541-50. (PMID: 20685997)
J Huntingtons Dis. 2013;2(2):201-15. (PMID: 24683430)
Mol Biol Cell. 2016 Jul 1;27(13):2025-36. (PMID: 27170182)
J Alzheimers Dis. 2017;59(2):575-590. (PMID: 28598849)
Neurobiol Aging. 2017 Jan;49:214.e1-214.e5. (PMID: 27480424)
Brain Res. 2015 Feb 9;1597:37-46. (PMID: 25511991)
PLoS One. 2014 Jan 27;9(1):e87513. (PMID: 24475300)
Neuron. 1997 Aug;19(2):333-44. (PMID: 9292723)
PLoS Biol. 2018 Jul 3;16(7):e2005970. (PMID: 29969450)
J Biol Chem. 2013 Nov 29;288(48):34460-9. (PMID: 24106274)
J Biol Chem. 2001 Nov 30;276(48):44889-97. (PMID: 11572863)
Biochim Biophys Acta Gen Subj. 2019 Oct;1863(10):1568-1574. (PMID: 31175912)
J Alzheimers Dis. 2004 Feb;6(1):79-92. (PMID: 15004330)
Mol Brain. 2015 Oct 31;8(1):71. (PMID: 26521126)
Proc Natl Acad Sci U S A. 2014 Apr 15;111(15):5706-11. (PMID: 24706802)
Biochimie. 2001 Mar-Apr;83(3-4):289-93. (PMID: 11295488)
Hum Mol Genet. 2010 Oct 1;19(19):3702-20. (PMID: 20616151)
Nat Methods. 2012 Mar 18;9(5):467-70. (PMID: 22426490)
Cell Rep. 2019 Apr 23;27(4):1133-1150.e8. (PMID: 31018129)
Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4199-E4208. (PMID: 29666234)
J Cell Biol. 2006 Sep 25;174(7):963-71. (PMID: 17000876)
Hum Mol Genet. 2000 Mar 1;9(4):503-13. (PMID: 10699173)
Cell Mol Life Sci. 2019 Dec 4;:. (PMID: 31802140)
Nucleus. 2011 Jul-Aug;2(4):258-63. (PMID: 21941109)
Acta Neuropathol Commun. 2018 Nov 8;6(1):122. (PMID: 30409191)
Cell. 2016 Aug 11;166(4):935-949. (PMID: 27477512)
J Mol Biol. 2008 Mar 14;377(1):162-80. (PMID: 18241885)
Brain Pathol. 2017 May;27(3):345-355. (PMID: 27377427)
Mol Ther. 2013 Oct;21(10):1898-908. (PMID: 23765441)
Proc Natl Acad Sci U S A. 2018 Oct 30;115(44):E10495-E10504. (PMID: 30333186)
EMBO J. 2009 Feb 18;28(4):372-82. (PMID: 19153604)
J Neurosci. 1999 Dec 1;19(23):10338-47. (PMID: 10575031)
معلومات مُعتمدة: P30 AG053760 United States AG NIA NIH HHS; R01 NS097542 United States NS NINDS NIH HHS; F32 AG059362 United States AG NIA NIH HHS; R01 NS096785 United States NS NINDS NIH HHS; T32 NS007222 United States NS NINDS NIH HHS; R01 NS038712 United States NS NINDS NIH HHS; R01 NS113943 United States NS NINDS NIH HHS
المشرفين على المادة: 0 (Adaptor Proteins, Signal Transducing)
0 (Autophagy-Related Proteins)
0 (Htt protein, mouse)
0 (Huntingtin Protein)
0 (Peptides)
0 (UBQLN2 protein, mouse)
26700-71-0 (polyglutamine)
EC 3.4.19.12 (Ataxin-3)
EC 3.4.19.12 (Atxn3 protein, mouse)
EC 3.4.25.1 (Proteasome Endopeptidase Complex)
تواريخ الأحداث: Date Created: 20200719 Date Completed: 20210830 Latest Revision: 20210830
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC7471500
DOI: 10.1093/hmg/ddaa152
PMID: 32681165
قاعدة البيانات: MEDLINE
الوصف
تدمد:1460-2083
DOI:10.1093/hmg/ddaa152