Ubiquitin-binding site 2 of ataxin-3 prevents its proteasomal degradation by interacting with Rad23

Nature Communications

Volumn 5, Issue , 2014, Pages

  Blount, Jessica R ^a   Tsou, Wei Ling ^a   Ristic, Gorica ^a   Burr, Aaron A ^a   Ouyang, Michelle ^a   Galante, Holland ^b   Scaglione, K Matthew ^b   Todi, Sokol V ^a  

^a WAYNE STATE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b MEDICAL COLLEGE OF WISCONSIN   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ATAXIN 3; CELL PROTEIN; PROTEASOME; RAD23 PROTEIN; UBIQUITIN; UBIQUITIN BINDING SITE 2; UNCLASSIFIED DRUG; ATXN3 PROTEIN, HUMAN; DNA BINDING PROTEIN; DNA LIGASE; RAD23A PROTEIN, HUMAN; REPRESSOR PROTEIN;

ANIMAL; BIODEGRADATION; ENZYME ACTIVITY; FLY; MAMMAL; MUTATION; PROTEIN;

AMINO TERMINAL SEQUENCE; ANIMAL TISSUE; ARTICLE; CELL CULTURE; CONTROLLED STUDY; DEGENERATION; DROSOPHILA MELANOGASTER; HUMAN; HUMAN CELL; MAMMAL CELL; MUTATION; NONHUMAN; PROTEIN DEGRADATION; PROTEIN PROTEIN INTERACTION; PROTEIN TARGETING; UBIQUITINATION; ANIMAL; BINDING SITE; GENE SILENCING; GENETICS; HELA CELL LINE; METABOLISM; TRANSGENIC ANIMAL;

ANIMALS; ANIMALS, GENETICALLY MODIFIED; ATAXIN-3; BINDING SITES; DNA REPAIR ENZYMES; DNA-BINDING PROTEINS; DROSOPHILA MELANOGASTER; GENE KNOCKDOWN TECHNIQUES; HELA CELLS; HUMANS; PROTEASOME ENDOPEPTIDASE COMPLEX; REPRESSOR PROTEINS; UBIQUITIN; UBIQUITINATION;

EID: 84907313542     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/ncomms5638     Document Type: Article

References (55)

1. Costa Mdo, C. & Paulson, H. L. Toward understanding Machado-Joseph disease. Prog. Neurobiol. 97, 239-257 (2012).
2. Todi, S. V., Williams, A. & Paulson, H. L. in Molecular Neurology 1st edn (ed. Waxman, S. G.) (Academic Press, 2007).
3. Williams, A. J. & Paulson, H. L. Polyglutamine neurodegeneration: protein misfolding revisited. Trends Neurosci. 31, 521-528 (2008).
4. Orr, H. T. & Zoghbi, H. Y. Trinucleotide repeat disorders. Ann. Rev. Neurosci. 30, 575-621 (2007). (Pubitemid 47218768)
5. Reina, C. P., Zhong, X. & Pittman, R. N. Proteotoxic stress increases nuclear localization of ataxin-3. Hum. Mol. Genet. 19, 235-249 (2010).
6. Warrick, J. M. et al. Ataxin-3 suppresses polyglutamine neurodegeneration in Drosophila by a ubiquitin-associated mechanism. Mol. Cell 18, 37-48 (2005). (Pubitemid 40444646)
7. Tsou, W.-L. et al. Ubiquitination regulates the neuroprotective function of the deubiquitinase ataxin-3 in vivo. J. Biol. Chem. 288, 34460-34469 (2013).
8. Pedersen, J. T. & Heegaard, N. H. Analysis of protein aggregation in neurodegenerative disease. Anal. Chem. 85, 8254-8261 (2013).
9. Rodriguez-Lebron, E., Gouvion, C. M., Moore, S. A., Davidson, B. L. & Paulson, H. L. Allele-specific RNAi mitigates phenotypic progression in a transgenic model of Alzheimer's disease. Mol. Ther. 17, 1563-1573 (2009).
10. Alves, S. et al. Silencing ataxin-3 mitigates degeneration in a rat model of Machado-Joseph disease: no role for wild-type ataxin-3Hum. Mol. Genet. 19, 2380-2394 (2010).
11. Alves, S. et al. Striatal and nigral pathology in a lentiviral rat model of Machado-Joseph disease. Hum. Mol. Genet. 17, 2071-2083 (2008). (Pubitemid 351911977)
12. Williams, A. J., Knutson, T. M., Colomer Gould, V. F. & Paulson, H. L. In vivo suppression of polyglutamine neurotoxicity by C-terminus of Hsp70-interacting protein (CHIP) supports an aggregation model of pathogenesis. Neurobiol. Dis. 33, 342-353 (2009).
13. Harper, S. Q. et al. RNA interference improves motor and neuropathological abnormalities in a Huntington's disease mouse model. Proc. Natl Acad. Sci. USA 102, 5820-5825 (2005). (Pubitemid 40559643)
14. Xia, H. et al. RNAi suppresses polyglutamine-induced neurodegeneration in a model of spinocerebellar ataxia. Nat. Med. 10, 816-820 (2004). (Pubitemid 39070854)
15. Tsou, W. L., Soong, B. W., Paulson, H. L. & Rodriguez-Lebron, E. Splice isoform-specific suppression of the Cav2.1 variant underlying spinocerebellar ataxia type 6. Neurobiol. Dis. 43, 533-542 (2011).
16. Alves, S. et al. Allele-specific RNA silencing of mutant ataxin-3 mediates neuroprotection in a rat model of Machado-Joseph disease. PLoS ONE 3, e3341 (2008).
17. Bove, J., Martinez-Vicente, M. & Vila, M. Fighting neurodegeneration with rapamycin: mechanistic insights. Nat. Rev. Neurosci. 12, 437-452 (2011).
18. do Carmo Costa, M. et al. Toward RNAi therapy for the polyglutamine disease Machado-Joseph disease. Mol. Ther. 21, 1898-1908 (2013).
19. Nobrega, C. et al. Silencing mutant ataxin-3 rescues motor deficits and neuropathology in machado-joseph disease transgenic mice. PLoS ONE 8, e52396 (2013).
20. Heride, C., Urbe, S. & Clague, M. J. Ubiquitin code assembly and disassembly. Curr. Biol. 24, 215-220 (2014).
21. Nicastro, G. et al. Josephin domain of ataxin-3 contains two distinct ubiquitinbinding sites. Biopolymers 91, 1203-1214 (2009).
22. Nicastro, G. et al. The solution structure of the Josephin domain of ataxin-3: structural determinants for molecular recognition. Proc. Natl Acad. Sci. USA 102, 10493-10498 (2005). (Pubitemid 41061582)
23. Nicastro, G. et al. Understanding the role of the Josephin domain in the PolyUb binding and cleavage properties of ataxin-3. PLoS ONE 5, e12430 (2010).
24. Wang, G., Sawai, N., Kotliarova, S., Kanazawa, I. & Nukina, N. Ataxin-3, the MJD1 gene product, interacts with the two human homologs of yeast DNA repair protein RAD23, HHR23A and HHR23B. Hum. Mol. Genet. 9, 1795-1803 (2000). (Pubitemid 30608613)
25. Todi, S. V. et al. Cellular turnover of the polyglutamine disease protein ataxin-3 is regulated by its catalytic activity. J. Biol. Chem. 282, 29348-29358 (2007). (Pubitemid 350043336)
26. Todi, S. V. et al. Ubiquitination directly enhances activity of the deubiquitinating enzyme ataxin-3. EMBO J. 28, 372-382 (2009).
27. Todi, S. V. et al. Activity and cellular functions of the deubiquitinating enzyme and polyglutamine disease protein ataxin-3 are regulated by ubiquitination at lysine 117. J. Biol. Chem. 285, 39303-39313 (2010).
28. Scaglione, K. M. et al. Ube2w and ataxin-3 coordinately regulate the ubiquitin ligase CHIP. Mol. Cell 43, 599-612 (2011).
29. Winborn, B. J. et al. The deubiquitinating enzyme ataxin-3, a polyglutamine disease protein, edits Lys63 linkages in mixed linkage ubiquitin chains. J. Biol. Chem. 283, 26436-26443 (2008).
30. Brand, A. H. & Perrimon, N. Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development 118, 401-415 (1993). (Pubitemid 23214028)
31. Todi, S. V., Franke, J. D., Kiehart, D. P. & Eberl, D. F. Myosin VIIA defects, which underlie the Usher 1B syndrome in humans, lead to deafness in Drosophila. Curr. Biol. 15, 862-868 (2005). (Pubitemid 40697264)
32. Franke, J. D., Boury, A. L., Gerald, N. J. & Kiehart, D. P. Native nonmuscle myosin II stability and light chain binding in Drosophila melanogaster. Cell Motil. Cytoskeleton 63, 604-622 (2006). (Pubitemid 44454022)
33. Buchberger, A., Bukau, B. & Sommer, T. Protein quality control in the cytosol and the endoplasmic reticulum: brothers in arms. Mol. Cell 40, 238-252 (2010).
34. Dantuma, N. P., Heinen, C. & Hoogstraten, D. The ubiquitin receptor Rad23: at the crossroads of nucleotide excision repair and proteasomal degradation. DNA Repair (Amst) 8, 449-460 (2009).
35. Boeddrich, A. et al. An arginine/lysine-rich motif is crucial for VCP/p97-mediated modulation of ataxin-3 fibrillogenesis. EMBO J. 25, 1547-1558 (2006).
36. Morreale, G., Conforti, L., Coadwell, J., Wilbrey, A. L. & Coleman, M. P. Evolutionary divergence of valosin-containing protein/cell division cycle protein 48 binding interactions among endoplasmic reticulum-associated degradation proteins. FEBS J. 276, 1208-1220 (2009).
37. Zhong, X. & Pittman, R. N. Ataxin-3 binds VCP/p97 and regulates retrotranslocation of ERAD substrates. Hum. Mol. Genet. 15, 2409-2420 (2006). (Pubitemid 44288695)
38. Shoesmith Berke, S. J., Chai, Y., Marrs, G. L., Wen, H. & Paulson, H. L. Defining the role of ubiquitin interacting motifs in the polyglutamine disease protein, ataxin-3. J. Biol. Chem. 280, 32026-32034 (2005). (Pubitemid 41291954)
39. A database of Drosophila genes & genomes. Flybase.org (2014).
40. Jana, N. R. et al. Co-chaperone CHIP associates with expanded polyglutamine protein and promotes their degradation by proteasomes. J. Biol. Chem. 280, 11635-11640 (2005). (Pubitemid 40418477)
41. Sheaff, R. J. et al. Proteasomal turnover of p21Cip1 does not require p21Cip1 ubiquitination. Mol. Cell 5, 403-410 (2000). (Pubitemid 30628097)
42. Tarcsa, E., Szymanska, G., Lecker, S., O'Connor, C. M. & Goldberg, A. L. Ca2\+-free calmodulin and calmodulin damaged by in vitro aging are selectively degraded by 26 S proteasomes without ubiquitination. J. Biol. Chem. 275, 20295-20301 (2000). (Pubitemid 30457603)
43. Forsthoefel, A. M., Pena, M. M., Xing, Y. Y., Rafique, Z. & Berger, F. G. Structural determinants for the intracellular degradation of human thymidylate synthase. Biochemistry 43, 1972-1979 (2004). (Pubitemid 38233259)
44. Blair, L. J. et al. Accelerated neurodegeneration through chaperone-mediated oligomerization of tau. J. Clin. Invest. 123, 4158-4169 (2013).
45. Hoyt, M. A. & Coffino, P. Ubiquitin-free routes into the proteasome. Cell. Mol. Life Sci. 61, 1596-1600 (2004). (Pubitemid 38962042)
46. Lim, J. et al. A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration. Cell 125, 801-814 (2006). (Pubitemid 43732348)
47. Sacco, J. J. et al. The deubiquitylase Ataxin-3 restricts PTEN transcription in lung cancer cells. Oncogene 33, 4265-4272 (2014).
48. Song, M. S., Salmena, L. & Pandolfi, P. P. The functions and regulation of the PTEN tumour suppressor. Nat. Rev. Mol. Cell. Biol. 13, 283-296 (2012).
49. Leslie, N. R. & Foti, M. Non-genomic loss of PTEN function in cancer: not in my genes. Trends Pharmacol. Sci. 32, 131-140 (2011).
50. Claessen, J. H., Kundrat, L. & Ploegh, H. L. Protein quality control in the ER: balancing the ubiquitin checkbook. Trends Cell Biol. 22, 22-32 (2012).
51. Yamanaka, K., Sasagawa, Y. & Ogura, T. Recent advances in p97/VCP/Cdc48 cellular functions. Biochim. Biophys. Acta 1823, 130-137 (2012).
52. Blount, J. R., Burr, A. A., Denuc, A., Marfany, G. & Todi, S. V. Ubiquitinspecific protease 25 functions in Endoplasmic Reticulum-associated degradation. PLoS ONE 7, e36542 (2012).
53. Paulson, H. L. et al. Intranuclear inclusions of expanded polyglutamine protein in spinocerebellar ataxia type 3. Neuron 19, 333-344 (1997). (Pubitemid 27374232)
54. Tsou, W.-L. et al. Systematic analysis of the physiological importance of deubiquitinating enzymes. PLoS ONE 7, e43112 (2012).
55. Scaglione, K. M. et al. The ubiquitin-conjugating enzyme (E2) Ube2w ubiquitinates the N terminus of substrates. J. Biol. Chem. 288, 18784-18788 (2013).