Ubiquitin hydrolase UCH-L1 destabilizes mTOR complex 1 by antagonizing DDB1-CUL4-mediated ubiquitination of raptor

Molecular and Cellular Biology

Volumn 33, Issue 6, 2013, Pages 1188-1197

  Hussain, Sajjad ^a   Feldman, Andrew ^b   Das, Chittaranjan ^c   Ziesmer, Steven ^b   Ansell, Stephen ^b   Galardy, Paul ^a,b,d  

^a Mayo ClinicHiroshima University   (United States)

^b MAYO CLINIC   (United States)

^c PURDUE UNIVERSITY   (United States)

^d MAYO GRADUATE SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CULLIN 4; DDB1 PROTEIN; HYDROLASE; INITIATION FACTOR 4E BINDING PROTEIN 1; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 2; PROTEIN KINASE B; REGULATOR PROTEIN; S6 KINASE; UBIQUITIN; UBIQUITIN PROTEIN LIGASE; UCH L1 PROTEIN; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; COMPLEX FORMATION; CONTROLLED STUDY; DISSOLUTION; ENZYME ACTIVITY; FEMALE; HUMAN; HUMAN CELL; MOUSE; NERVE DEGENERATION; NONHUMAN; PRIORITY JOURNAL; PROTEIN ASSEMBLY; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; PROTEIN STABILITY; SIGNAL TRANSDUCTION; TRANSCRIPTION REGULATION; UBIQUITINATION;

ANIMALS; CATALYSIS; CELL LINE; DNA-BINDING PROTEINS; HYDROLASES; MICE; MICE, TRANSGENIC; MULTIPROTEIN COMPLEXES; PROTEINS; PROTO-ONCOGENE PROTEINS C-AKT; RIBOSOMAL PROTEIN S6 KINASES; SIGNAL TRANSDUCTION; TOR SERINE-THREONINE KINASES; UBIQUITIN; UBIQUITIN THIOLESTERASE; UBIQUITINATION;

EID: 84874685418     PISSN: 02707306     EISSN: 10985549     Source Type: Journal    
DOI: 10.1128/MCB.01389-12     Document Type: Article

References (41)

1. Zoncu R, Efeyan A, Sabatini DM. 2011. mTOR: from growth signal integration to cancer, diabetes and ageing. Nat. Rev. Mol. Cell Biol. 12:21-35.
2. Hussain S, Foreman O, Perkins SL, Witzig TE, Miles RR, van Deursen J, Galardy PJ. 2010. The de-ubiquitinase UCH-L1 is an oncogene that drives the development of lymphoma in vivo by deregulating PHLPP1 and Akt signaling. Leukemia 24:1641-1655.
3. Wilson PO, Barber PC, Hamid QA, Power BF, Dhillon AP, Rode J, Day IN, Thompson RJ, Polak JM. 1988. The immunolocalization of protein gene product 9.5 using rabbit polyclonal and mouse monoclonal antibodies. Br. J. Exp. Pathol. 69:91-104.
4. Saigoh K, Wang YL, Suh JG, Yamanishi T, Sakai Y, Kiyosawa H, Harada T, Ichihara N, Wakana S, Kikuchi T, Wada K. 1999. Intragenic deletion in the gene encoding ubiquitin carboxy-terminal hydrolase in gad mice. Nat. Genet. 23:47-51.
5. Maraganore DM, Lesnick TG, Elbaz A, Chartier-Harlin MC, Gasser T, Kruger R, Hattori N, Mellick GD, Quattrone A, Satoh J, Toda T, Wang J, Ioannidis JP, de Andrade M, Rocca WA. 2004. UCHL1 is a Parkinson's disease susceptibility gene. Ann. Neurol. 55:512-521.
6. Ragland M, Hutter C, Zabetian C, Edwards K. 2009. Association between the ubiquitin carboxyl-terminal esterase L1 gene (UCHL1) S18Y variant and Parkinson's disease: a HuGE review and meta-analysis. Am. J. Epidemiol. 170:1344-1357.
7. Ovaa H, Kessler BM, Rolen U, Galardy PJ, Ploegh HL, Masucci MG. 2004. Activity-based ubiquitin-specific protease (USP) profiling of virusinfected and malignant human cells. Proc. Natl. Acad. Sci. U. S. A. 101: 2253-2258.
8. Otsuki T, Yata K, Takata-Tomokuni A, Hyodoh F, Miura Y, Sakaguchi H, Hatayama T, Hatada S, Tsujioka T, Sato Y, Murakami H, Sadahira Y, Sugihara T. 2004. Expression of protein gene product 9.5 (PGP9.5)/ubiquitin-C-terminal hydrolase 1 (UCHL-1) in human myeloma cells. Br. J. Haematol. 127:292-298.
9. Hibi K, Westra WH, Borges M, Goodman S, Sidransky D, Jen J. 1999. PGP9.5 as a candidate tumor marker for non-small-cell lung cancer. Am. J. Pathol. 155:711-715.
10. Miest T, Saenz D, Meehan A, Llano M, Poeschla EM. 2009. Intensive RNAi with lentiviral vectors in mammalian cells. Methods 47:298-303.
11. Liu E, Knutzen CA, Krauss S, Schweiger S, Chiang GG. 2011. Control of mTORC1 signaling by the Opitz syndrome protein MID1. Proc. Natl. Acad. Sci. U. S. A. 108:8680-8685.
12. Sarbassov DD, Ali SM, Sengupta S, Sheen JH, Hsu PP, Bagley AF, Markhard AL, Sabatini DM. 2006. Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB. Mol. Cell 22:159-168.
13. Sancak Y, Thoreen CC, Peterson TR, Lindquist RA, Kang SA, Spooner E, Carr SA, Sabatini DM. 2007. PRAS40 is an insulin-regulated inhibitor of the mTORC1 protein kinase. Mol. Cell 25:903-915.
14. Walters BJ, Campbell SL, Chen PC, Taylor AP, Schroeder DG, Dobrunz LE, Artavanis-Tsakonas K, Ploegh HL, Wilson JA, Cox GA, Wilson SM. 2008. Differential effects of Usp14 and Uch-L1 on the ubiquitin proteasome system and synaptic activity. Mol. Cell Neurosci. 39:539-548.
15. Taylor SS, Hussein D, Wang Y, Elderkin S, Morrow CJ. 2001. Kinetochore localisation and phosphorylation of the mitotic checkpoint components Bub1 and BubR1 are differentially regulated by spindle events in human cells. J. Cell Sci. 114:4385-4395.
16. Sancak Y, Bar-Peled L, Zoncu R, Markhard AL, Nada S, Sabatini DM. 2010. Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids. Cell 141:290-303.
17. Alessi DR, Andjelkovic M, Caudwell B, Cron P, Morrice N, Cohen P, Hemmings BA. 1996. Mechanism of activation of protein kinase B by insulin and IGF-1. EMBO J. 15:6541-6551.
18. Sarbassov DD, Ali SM, Kim DH, Guertin DA, Latek RR, Erdjument-Bromage H, Tempst P, Sabatini DM. 2004. Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptorindependent pathway that regulates the cytoskeleton. Curr. Biol. 14: 1296-1302.
19. Liu J, Stevens PD, Gao T. 2011. mTOR-dependent regulation of PHLPP expression controls the rapamycin sensitivity in cancer cells. J. Biol. Chem. 286:6510-6520.
20. Harrington LS, Findlay GM, Gray A, Tolkacheva T, Wigfield S, Rebholz H, Barnett J, Leslie NR, Cheng S, Shepherd PR, Gout I, Downes CP, Lamb RF. 2004. The TSC1-2 tumor suppressor controls insulin-PI3K signaling via regulation of IRS proteins. J. Cell Biol. 166:213-223.
21. O'Reilly KE, Rojo F, She QB, Solit D, Mills GB, Smith D, Lane H, Hofmann F, Hicklin DJ, Ludwig DL, Baselga J, Rosen N. 2006. mTOR inhibition induces upstream receptor tyrosine kinase signaling and activates Akt. Cancer Res. 66:1500-1508.
22. Fingar DC, Salama S, Tsou C, Harlow E, Blenis J. 2002. Mammalian cell size is controlled by mTOR and its downstream targets S6K1 and 4EBP1/eIF4E. Genes Dev. 16:1472-1487.
23. Sancak Y, Peterson TR, Shaul YD, Lindquist RA, Thoreen CC, Bar-Peled L, Sabatini DM. 2008. The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1. Science 320:1496-1501.
24. Ghosh P, Wu M, Zhang H, Sun H. 2008. mTORC1 signaling requires proteasomal function and the involvement of CUL4-DDB1 ubiquitin E3 ligase. Cell Cycle 7:373-381.
25. Li J, Wang QE, Zhu Q, El-Mahdy MA, Wani G, Praetorius-Ibba M, Wani AA. 2006. DNA damage binding protein component DDB1 participates in nucleotide excision repair through DDB2 DNA-binding and cullin 4A ubiquitin ligase activity. Cancer Res. 66:8590-8597.
26. Lee J, Zhou P. 2007. DCAFs, the missing link of the CUL4-DDB1 ubiquitin ligase. Mol. Cell 26:775-780.
27. Hodgins RR, Ellison KS, Ellison MJ. 1992. Expression of a ubiquitin derivative that conjugates to protein irreversibly produces phenotypes consistent with a ubiquitin deficiency. J. Biol. Chem. 267:8807-8812.
28. Colland F. 2010. The therapeutic potential of deubiquitinating enzyme inhibitors. Biochem. Soc. Trans. 38:137-143.
29. Love KR, Catic A, Schlieker C, Ploegh HL. 2007. Mechanisms, biology and inhibitors of deubiquitinating enzymes. Nat. Chem. Biol. 3:697-705.
30. Nag DK, Finley D. 2012. A small-molecule inhibitor of deubiquitinating enzyme USP14 inhibits Dengue virus replication. Virus Res. 165:103-106.
31. Reverdy C, Conrath S, Lopez R, Planquette C, Atmanene C, Collura V, Harpon J, Battaglia V, Vivat V, Sippl W, Colland F. 2012. Discovery of specific inhibitors of human USP7/HAUSP deubiquitinating enzyme. Chem. Biol. 19:467-477.
32. Zhao Y, Xiong X, Jia L, Sun Y. 2012. Targeting Cullin-RING ligases by MLN4924 induces autophagy via modulating the HIF1-REDD1-TSC1-mTORC1-DEPTOR axis. Cell Death Dis. 3:e386. doi:10.1038/cddis.2012 .125.
33. Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP. 2011. Systematic and quantitative assessment of the ubiquitin-modified proteome. Mol. Cell 44:325-340.
34. Sarbassov DD, Guertin DA, Ali SM, Sabatini DM. 2005. Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science 307:1098-1101.
35. Copp J, Manning G, Hunter T. 2009. TORC-specific phosphorylation of mammalian target of rapamycin (mTOR): phospho-Ser2481 is a marker for intact mTOR signaling complex 2. Cancer Res. 69:1821-1827.
36. Soliman GA, Acosta-Jaquez HA, Dunlop EA, Ekim B, Maj NE, Tee AR, Fingar DC. 2010. mTOR Ser-2481 autophosphorylation monitors mTORC-specific catalytic activity and clarifies rapamycin mechanism of action. J. Biol. Chem. 285:7866-7879.
37. Plank TL, Logginidou H, Klein-Szanto A, Henske EP. 1999. The expression of hamartin, the product of the TSC1 gene, in normal human tissues and in TSC1-and TSC2-linked angiomyolipomas. Mod. Pathol. 12:539-545.
38. Sampson JR. 2009. Therapeutic targeting of mTOR in tuberous sclerosis. Biochem. Soc. Trans. 37:259-264.
39. Leroy E, Boyer R, Auburger G, Leube B, Ulm G, Mezey E, Harta G, Brownstein MJ, Jonnalagada S, Chernova T, Dehejia A, Lavedan C, Gasser T, Steinbach PJ, Wilkinson KD, Polymeropoulos MH. 1998. The ubiquitin pathway in Parkinson's disease. Nature 395:451-452.
40. Ehninger D, Han S, Shilyansky C, Zhou Y, Li W, Kwiatkowski DJ, Ramesh V, Silva AJ. 2008. Reversal of learning deficits in a Tsc2 mouse model of tuberous sclerosis. Nat. Med. 14:843-848.
41. Tain LS, Mortiboys H, Tao RN, Ziviani E, Bandmann O, Whitworth AJ. 2009. Rapamycin activation of 4E-BP prevents parkinsonian dopaminergic neuron loss. Nat. Neurosci. 12:1129-1135.