Deubiquitinase inhibition by WP1130 leads to ULK1 aggregation and blockade of autophagy

Autophagy

Volumn 11, Issue 9, 2015, Pages 1458-1470

  Drießen, Stefan ^a   Berleth, Niklas ^a   Friesen, Olena ^a   Löffler, Antje S ^a   Böhler, Philip ^a   Hieke, Nora ^a   Stuhldreier, Fabian ^a   Peter, Christoph ^a   Schink, Kay O ^b   Schultz, Sebastian W ^b   Stenmark, Harald ^b   Holland, Petter ^c   Simonsen, Anne ^c   Wesselborg, Sebastian ^a   Stork, Björn ^a  

^a HEINRICH HEINE UNIVERSITY   (Germany)

^b OSLO UNIVERSITY HOSPITAL   (Norway)

^c UNIVERSITY OF OSLO   (Norway)

Author keywords

Autophagy; Deubiquitinases; Ubiquitination; ULK1; WP1130

Indexed keywords

DEUBIQUITINASE; ENZYME INHIBITOR; PROTEIN SERINE THREONINE KINASE; PROTEIN SERINE THREONINE KINASE ULK1; UNCLASSIFIED DRUG; WP 1130; CYANOACRYLATE DERIVATIVE; DEGRASYN; GREEN FLUORESCENT PROTEIN; PROTEIN AGGREGATE; PYRIDINE DERIVATIVE; SERINE THREONINE PROTEIN KINASE ULK1; SIGNAL PEPTIDE; ULK1 PROTEIN, HUMAN;

AGGRESOME; ARTICLE; AUTOPHAGY; ENZYME ACTIVITY; ENZYME INHIBITION; PROTEIN AGGREGATION; PROTEIN TRANSPORT; UBIQUITINATION; ANTAGONISTS AND INHIBITORS; DRUG EFFECTS; HEK293 CELL LINE; HELA CELL LINE; HUMAN; METABOLISM;

AUTOPHAGY; AUTOPHAGY-RELATED PROTEIN-1 HOMOLOG; CYANOACRYLATES; GREEN FLUORESCENT PROTEINS; HEK293 CELLS; HELA CELLS; HUMANS; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; PROTEIN AGGREGATES; PROTEIN-SERINE-THREONINE KINASES; PYRIDINES; UBIQUITIN-SPECIFIC PROTEASES; UBIQUITINATION;

EID: 84947583662     PISSN: 15548627     EISSN: 15548635     Source Type: Journal    
DOI: 10.1080/15548627.2015.1067359     Document Type: Article

References (38)

1. Mizushima N, Yoshimori T, Ohsumi Y. The role of Atg proteins in autophagosome formation. Annu Rev Cell Dev Biol 2011; 27:107-32; PMID:21801009; http://dx.doi.org/10.1146/annurev-cellbio-092910-154005
2. Alers S, Löffler AS, Wesselborg S, Stork B. Role of AMPK-mTOR-Ulk1/2 in the regulation of autophagy: cross talk, shortcuts, and feedbacks. Mol Cell Biol 2012; 32:2-11; PMID:22025673; http://dx.doi.org/10.1128/MCB.06159-11
3. Chan EY, Longatti A, McKnight NC, Tooze SA. Kinase-inactivated ULK proteins inhibit autophagy via their conserved C-terminal domains using an Atg13- independent mechanism. Mol Cell Biol 2009; 29:157-71;PMID:18936157; http://dx.doi.org/10.1128/MCB.01082-08
4. Ganley IG, Lam du H, Wang J, Ding X, Chen S, Jiang X. ULK1.ATG13.FIP200 complex mediates mTOR signaling and is essential for autophagy. J Biol Chem 2009; 284:12297-305; PMID:19258318
5. Hosokawa N, Hara T, Kaizuka T, Kishi C, Takamura A, Miura Y, Iemura S, Natsume T, Takehana K, Yamada N, et al. Nutrient-dependent mTORC1 association with the ULK1-Atg13-FIP200 complex required for autophagy. Mol Biol Cell 2009; 20:1981-91; PMID:19211835;http://dx.doi.org/10.1091/mbc.E08-12-1248
6. Jung CH, Jun CB, Ro SH, Kim YM, Otto NM, Cao J, Kundu M, Kim DH. ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. Mol Biol Cell 2009; 20:1992-2003; PMID:19225151; http://dx.doi.org/10.1091/mbc.E08-12-1249
7. Alers S, Löffler AS, Wesselborg S, Stork B. The incredible ULKs. Cell Commun Signal 2012; 10:7; PMID:22413737; http://dx.doi.org/10.1186/1478-811X-10-7
8. Chan EY. mTORC1 phosphorylates the ULK1- mAtg13-FIP200 autophagy regulatory complex. Sci Signal 2009; 2:pe51; PMID:19690328; http://dx.doi.org/10.1126/scisignal.284pe51
9. Chan EY, Tooze SA. Evolution of Atg1 function and regulation. Autophagy 2009; 5:758-65; PMID:19411825; http://dx.doi.org/10.4161/auto.8709
10. Mizushima N. The role of the Atg1/ULK1 complex in autophagy regulation. Curr Opin Cell Biol 2010; 22:132-9; PMID:20056399; http://dx.doi.org/10.1016/j.ceb.2009.12.004
11. Wong PM, Puente C, Ganley IG, Jiang X. The ULK1 complex: sensing nutrient signals for autophagy activation. Autophagy 2013; 9:124-37; PMID:23295650; http://dx.doi.org/10.4161/auto.23323
12. Alers S, Löffler AS, Paasch F, Dieterle AM, Keppeler H, Lauber K, Campbell DG, Fehrenbacher B, Schaller M, Wesselborg S, et al. Atg13 and FIP200 act independently of Ulk1 and Ulk2 in autophagy induction. Autophagy 2011; 7:1423-33; PMID:22024743; http://dx.doi.org/10.4161/auto.7.12.18027
13. Bach M, Larance M, James DE, Ramm G. The serine/ threonine kinase ULK1 is a target of multiple phosphorylation events. Biochem J 2011; 440:283-91; PMID:21819378; http://dx.doi.org/10.1042/BJ20101894
14. Egan DF, Shackelford DB, Mihaylova MM, Gelino S, Kohnz RA, Mair W, Vasquez DS, Joshi A, Gwinn DM, Taylor R, et al. Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy. Sci 2011; 331:456-61; PMID:21205641; http://dx.doi.org/10.1126/science.1196371
15. Kim J, Kundu M, Viollet B, Guan KL. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol 2011; 13:132-41; PMID:21258367; http://dx.doi.org/10.1038/ncb2152
16. Mack HI, Zheng B, Asara JM, Thomas SM. AMPKdependent phosphorylation of ULK1 regulates ATG9 localization. Autophagy 2012; 8:1197-214; PMID:22932492; http://dx.doi.org/10.4161/auto. 20586
17. Shang L, Chen S, Du F, Li S, Zhao L, Wang X. Nutrient starvation elicits an acute autophagic response mediated by Ulk1 dephosphorylation and its subsequent dissociation from AMPK. Proc Natl Acad Sci U S A 2011; 108:4788-93; PMID:21383122; http://dx.doi.org/10.1073/pnas.1100844108
18. Lin SY, Li TY, Liu Q, Zhang C, Li X, Chen Y, Zhang SM, Lian G, Ruan K, Wang Z, et al. GSK3-TIP60- ULK1 signaling pathway links growth factor deprivation to autophagy. Sci 2012; 336:477-81;PMID:22539723; http://dx.doi.org/10.1126/science.1217032
19. Nazio F, Strappazzon F, Antonioli M, Bielli P, Cianfanelli V, Bordi M, Gretzmeier C, Dengjel J, Piacentini M, Fimia GM, et al. mTOR inhibits autophagy by controlling ULK1 ubiquitylation, self-association and function through AMBRA1 and TRAF6. Nat Cell Biol 2013; 15:406-16; PMID:23524951; http://dx.doi.org/10.1038/ncb2708
20. Di Bartolomeo S, CorazzariM,Nazio F, Oliverio S, Lisi G, AntonioliM, Pagliarini V,Matteoni S, Fuoco C, Giunta L, et al.The dynamic interaction ofAMBRA1with the dynein motor complex regulates mammalian autophagy. JCell Biol 2010; 191:155-68; PMID:20921139; http://dx.doi.org/10.1083/jcb.201002100
21. Russell RC, Tian Y, Yuan H, Park HW, Chang YY, Kim J, Kim H, Neufeld TP, Dillin A, Guan KL. ULK1 induces autophagy by phosphorylating Beclin-1 and activating VPS34 lipid kinase. Nat Cell Biol 2013; 15:741-50; PMID:23685627; http://dx.doi.org/10.1038/ncb2757
22. Tang HW, Wang YB, Wang SL, Wu MH, Lin SY, Chen GC. Atg1-mediated myosin II activation regulates autophagosome formation during starvationinduced autophagy. EMBO J 2011; 30:636-51; PMID:21169990; http://dx.doi.org/10.1038/emboj.2010.338
23. Papinski D, Schuschnig M, Reiter W, Wilhelm L, Barnes CA, Maiolica A, Hansmann I, Pfaffenwimmer T, Kijanska M, Stoffel I, et al. Early steps in autophagy depend on direct phosphorylation of atg9 by the atg1 kinase. Mole Cell 2014; 53:471-83; PMID:24440502; http://dx.doi.org/10.1016/j.molcel.2013.12.011
24. Löffler AS, Alers S, Dieterle AM, Keppeler H, Franz- Wachtel M, Kundu M, Campbell DG, Wesselborg S, Alessi DR, Stork B. Ulk1-mediated phosphorylation of AMPK constitutes a negative regulatory feedback loop. Autophagy 2011; 7:696-706; PMID:21460634; http://dx.doi.org/10.4161/auto.7.7.15451
25. Bartholomeusz GA, Talpaz M, Kapuria V, Kong LY, Wang S, Estrov Z, Priebe W, Wu J, Donato NJ. Activation of a novel Bcr/Abl destruction pathway by WP1130 induces apoptosis of chronic myelogenous leukemia cells. Blood 2007; 109:3470-8; PMID:17202319; http://dx.doi.org/10.1182/blood-2006-02-005579
26. Kapuria V, Levitzki A, Bornmann WG, Maxwell D, Priebe W, Sorenson RJ, Showalter HD, Talpaz M, Donato NJ. A novel small molecule deubiquitinase inhibitor blocks Jak2 signaling through Jak2 ubiquitination. Cell Signal 2011; 23:2076-85; PMID:21855629; http://dx.doi.org/10.1016/j.cellsig.2011.08.002
27. Kapuria V, Peterson LF, Fang D, Bornmann WG, Talpaz M, Donato NJ. Deubiquitinase inhibition by small-molecule WP1130 triggers aggresome formation and tumor cell apoptosis. Cancer Res 2010; 70:9265- 76.;PMID:21045142; http://dx.doi.org/10.1158/0008-5472.CAN-10-1530
28. Sun H, Kapuria V, Peterson LF, Fang D, Bornmann WG, Bartholomeusz G, Talpaz M, Donato NJ. Bcr- Abl ubiquitination and Usp9x inhibition block kinase signaling and promote CML cell apoptosis. Blood 2011; 117:3151-62; PMID:21248063; http://dx.doi.org/10.1182/blood-2010-03-276477
29. Johnston JA, Ward CL, Kopito RR. Aggresomes: a cellular response to misfolded proteins. J Cell Biol 1998; 143:1883-98; PMID:9864362; http://dx.doi.org/10.1083/jcb.143.7.1883
30. Alemu EA, Lamark T, Torgersen KM, Birgisdottir AB, Larsen KB, Jain A, Olsvik H, Overvatn A, Kirkin V, Johansen T. ATG8 family proteins act as scaffolds for assembly of the ULK complex: sequence requirements for LC3-interacting region (LIR) motifs. J Biol Chem 2012; 287:39275-90; PMID:23043107; http://dx.doi.org/10.1074/jbc.M112.378109
31. Peddaboina C, Jupiter D, Fletcher S, Yap JL, Rai A, Tobin RP, Jiang W, Rascoe P, Rogers MK, Smythe WR, et al. The downregulation of Mcl-1 via USP9X inhibition sensitizes solid tumors to Bcl-xl inhibition. BMC Cancer 2012; 12:541; PMID:23171055; http://dx.doi.org/10.1186/1471-2407-12-541
32. Peng Z, Maxwell DS, Sun D, Bhanu Prasad BA, Schuber PT, Jr., Pal A, Ying Y, Han D, Gao L, Wang S, et al. Degrasyn-like symmetrical compounds: Possible therapeutic agents for multiple myeloma (MM-I). Bioorg Med Chem 2014; 22:1450-8; PMID:24457091; http://dx.doi.org/10.1016/j.bmc.2013.12.048
33. Wang S, Kollipara RK, Srivastava N, Li R, Ravindranathan P, Hernandez E, Freeman E, Humphries CG, Kapur P, Lotan Y, et al. Ablation of the oncogenic transcription factor ERG by deubiquitinase inhibition in prostate cancer. Proc Natl Acad Sci U S A 2014; 111 (11):4251-6; PMID:24591637; http://dx.doi.org/10.1073/pnas.1322198111
34. Harris DR, Mims A, Bunz F. Genetic disruption of USP9X sensitizes colorectal cancer cells to 5-fluorouracil. Cancer Biol Therapy 2012; 13:1319-24; PMID:22895071; http://dx.doi.org/10.4161/cbt.21792
35. Xu P, Duong DM, Seyfried NT, Cheng D, Xie Y, Robert J, Rush J, Hochstrasser M, Finley D, Peng J. Quantitative proteomics reveals the function of unconventional ubiquitin chains in proteasomal degradation. Cell 2009; 137:133-45; PMID:19345192; http://dx.doi.org/10.1016/j.cell.2009.01.041
36. Kobayashi S, Yoneda-Kato N, Itahara N, Yoshida A, Kato JY. The COP1 E3-ligase interacts with FIP200, a key regulator of mammalian autophagy. BMC Biochem 2013; 14:1; PMID:23289756; http://dx.doi.org/10.1186/1471-2091-14-1
37. Komander D, Clague MJ, Urbe S. Breaking the chains: structure and function of the deubiquitinases. Nat Rev Mol Cell Biol 2009; 10:550-63; PMID:19626045; http://dx.doi.org/10.1038/nrm2731
38. Lazarus MB, Novotny CJ, Shokat KM. Structure of the Human Autophagy Initiating Kinase ULK1 in Complex with Potent Inhibitors. ACS Chem Biol 2015; 10 (1):257-61; PMID:25551253; http://dx.doi.org/10.1021/cb500835z