Cul3-KLHL20 Ubiquitin Ligase Governs the Turnover of ULK1 and VPS34 Complexes to Control Autophagy Termination

Molecular Cell

Volumn 61, Issue 1, 2016, Pages 84-97

  Liu, Chin Chih ^a,b   Lin, Yu Ching ^a,b   Chen, Yu Hsuan ^a,b   Chen, Chun Ming ^a   Pang, Liang Yu ^a,c   Chen, Hsuan An ^a   Wu, Pei Rung ^a   Lin, Mei Yao ^a   Jiang, Si Tse ^d,f   Tsai, Ting Fen ^e   Chen, Ruey Hwa ^a,b,c  

^a INSTITUTE OF BIOLOGICAL CHEMISTRY   (Taiwan)

^b NATIONAL TAIWAN UNIVERSITY   (Taiwan)

^c NATIONAL TAIWAN UNIVERSITY   (Taiwan)

^d INSTITUTE OF MOLECULAR BIOLOGY   (Taiwan)

^e NATIONAL YANG MING UNIVERSITY   (Taiwan)

^f National Laboratory Animal Center   (Taiwan)

Author keywords

Autophagy; Ubiquitination; ULK1; VPS34 complex

Indexed keywords

BECLIN 1; CELL PROTEIN; CULLIN; CULLIN 3; KLHL20 UBIQUITIN LIGASE; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN ATG13; PROTEIN ATG14; PROTEIN SERINE THREONINE KINASE; UBIQUITIN PROTEIN LIGASE; ULK1 ENZYME; UNCLASSIFIED DRUG; APOPTOSIS REGULATORY PROTEIN; ATG14 PROTEIN, HUMAN; ATG14 PROTEIN, MOUSE; BECN1 PROTEIN, HUMAN; BECN1 PROTEIN, MOUSE; CARRIER PROTEIN; CUL3 PROTEIN, HUMAN; CUL3 PROTEIN, MOUSE; KLHL20 PROTEIN, HUMAN; KLHL20 PROTEIN, MOUSE; MEMBRANE PROTEIN; SIGNAL PEPTIDE; ULK1 PROTEIN, HUMAN; ULK1 PROTEIN, MOUSE; VESICULAR TRANSPORT ADAPTOR PROTEIN; VESICULAR TRANSPORT PROTEIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; AUTOPHAGY; AUTOPHOSPHORYLATION; CELL DEATH; COMPLEX FORMATION; CONTROLLED STUDY; ENZYME METABOLISM; HUMAN; HUMAN CELL; MOLECULAR DYNAMICS; MOUSE; MUSCLE ATROPHY; NONHUMAN; PROTEIN DEGRADATION; STREPTOZOTOCIN-INDUCED DIABETES MELLITUS; UBIQUITINATION; ANIMAL; C57BL MOUSE; DEFICIENCY; DIABETES MELLITUS; ENZYMOLOGY; FEEDBACK SYSTEM; GENETIC TRANSFECTION; GENETICS; HEK293 CELL LINE; HELA CELL LINE; KNOCKOUT MOUSE; MALE; METABOLISM; PATHOLOGY; PHOSPHORYLATION; PROTEIN TRANSPORT; RNA INTERFERENCE; SIGNAL TRANSDUCTION; SKELETAL MUSCLE; TIME FACTOR;

ADAPTOR PROTEINS, VESICULAR TRANSPORT; ANIMALS; APOPTOSIS REGULATORY PROTEINS; AUTOPHAGY; CARRIER PROTEINS; CLASS III PHOSPHATIDYLINOSITOL 3-KINASES; CULLIN PROTEINS; DIABETES COMPLICATIONS; FEEDBACK, PHYSIOLOGICAL; HEK293 CELLS; HELA CELLS; HUMANS; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; MALE; MEMBRANE PROTEINS; MICE, INBRED C57BL; MICE, KNOCKOUT; MUSCLE, SKELETAL; MUSCULAR ATROPHY; PHOSPHORYLATION; PROTEIN TRANSPORT; PROTEIN-SERINE-THREONINE KINASES; PROTEOLYSIS; RNA INTERFERENCE; SIGNAL TRANSDUCTION; TIME FACTORS; TRANSFECTION; UBIQUITIN-PROTEIN LIGASES; UBIQUITINATION; VESICULAR TRANSPORT PROTEINS;

EID: 84953637768     PISSN: 10972765     EISSN: 10974164     Source Type: Journal    
DOI: 10.1016/j.molcel.2015.11.001     Document Type: Article

References (51)

1. Alemu E.A., Lamark T., Torgersen K.M., Birgisdottir A.B., Larsen K.B., Jain A., Olsvik H., Øvervatn 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, 287:39275-39290.
2. Antonioli M., Albiero F., Nazio F., Vescovo T., Perdomo A.B., Corazzari M., Marsella C., Piselli P., Gretzmeier C., Dengjel J., et al. AMBRA1 interplay with cullin E3 ubiquitin ligases regulates autophagy dynamics. Dev. Cell 2014, 31:734-746.
3. Choi A.M., Ryter S.W., Levine B. Autophagy in human health and disease. N. Engl. J. Med. 2013, 368:651-662.
4. Di Bartolomeo S., Corazzari M., Nazio F., Oliverio S., Lisi G., Antonioli M., Pagliarini V., Matteoni S., Fuoco C., Giunta L., et al. The dynamic interaction of AMBRA1 with the dynein motor complex regulates mammalian autophagy. J. Cell Biol. 2010, 191:155-168.
5. Dorsey F.C., Rose K.L., Coenen S., Prater S.M., Cavett V., Cleveland J.L., Caldwell-Busby J. Mapping the phosphorylation sites of Ulk1. J. Proteome Res. 2009, 8:5253-5263.
6. Fan W., Nassiri A., Zhong Q. Autophagosome targeting and membrane curvature sensing by Barkor/Atg14(L). Proc. Natl. Acad. Sci. USA 2011, 108:7769-7774.
7. Feng Y., He D., Yao Z., Klionsky D.J. The machinery of macroautophagy. Cell Res. 2014, 24:24-41.
8. Füllgrabe J., Lynch-Day M.A., Heldring N., Li W., Struijk R.B., Ma Q., Hermanson O., Rosenfeld M.G., Klionsky D.J., Joseph B. The histone H4 lysine 16 acetyltransferase hMOF regulates the outcome of autophagy. Nature 2013, 500:468-471.
9. Ganley I.G., Lam 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, 284:12297-12305.
10. 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, 20:1981-1991.
11. Itakura E., Mizushima N. Characterization of autophagosome formation site by a hierarchical analysis of mammalian Atg proteins. Autophagy 2010, 6:764-776.
12. Itakura E., Kishi C., Inoue K., Mizushima N. Beclin 1 forms two distinct phosphatidylinositol 3-kinase complexes with mammalian Atg14 and UVRAG. Mol. Biol. Cell 2008, 19:5360-5372.
13. Jiang P., Mizushima N. Autophagy and human diseases. Cell Res. 2014, 24:69-79.
14. Joo J.H., Dorsey F.C., Joshi A., Hennessy-Walters K.M., Rose K.L., McCastlain K., Zhang J., Iyengar R., Jung C.H., Suen D.F., et al. Hsp90-Cdc37 chaperone complex regulates Ulk1- and Atg13-mediated mitophagy. Mol. Cell 2011, 43:572-585.
15. Jung C.H., Jun C.B., Ro S.H., Kim Y.M., Otto N.M., Cao J., Kundu M., Kim D.H. ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. Mol. Biol. Cell 2009, 20:1992-2003.
16. Kim J., Kundu M., Viollet B., Guan K.L. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat. Cell Biol. 2011, 13:132-141.
17. Kraft C., Kijanska M., Kalie E., Siergiejuk E., Lee S.S., Semplicio G., Stoffel I., Brezovich A., Verma M., Hansmann I., et al. Binding of the Atg1/ULK1 kinase to the ubiquitin-like protein Atg8 regulates autophagy. EMBO J. 2012, 31:3691-3703.
18. Kroemer G., Mariño G., Levine B. Autophagy and the integrated stress response. Mol. Cell 2010, 40:280-293.
19. Lee Y.R., Yuan W.C., Ho H.C., Chen C.H., Shih H.M., Chen R.H. The Cullin 3 substrate adaptor KLHL20 mediates DAPK ubiquitination to control interferon responses. EMBO J. 2010, 29:1748-1761.
20. Levine B., Kroemer G. Autophagy in the pathogenesis of disease. Cell 2008, 132:27-42.
21. Liang C. Negative regulation of autophagy. Cell Death Differ. 2010, 17:1807-1815.
22. Liu Y., Levine B. Autosis and autophagic cell death: the dark side of autophagy. Cell Death Differ. 2015, 22:367-376.
23. Liu J., Xia H., Kim M., Xu L., Li Y., Zhang L., Cai Y., Norberg H.V., Zhang T., Furuya T., et al. Beclin1 controls the levels of p53 by regulating the deubiquitination activity of USP10 and USP13. Cell 2011, 147:223-234.
24. Matsunaga K., Morita E., Saitoh T., Akira S., Ktistakis N.T., Izumi T., Noda T., Yoshimori T. Autophagy requires endoplasmic reticulum targeting of the PI3-kinase complex via Atg14L. J. Cell Biol. 2010, 190:511-521.
25. Mizushima N. The role of the Atg1/ULK1 complex in autophagy regulation. Curr. Opin. Cell Biol. 2010, 22:132-139.
26. Mizushima N. Autophagy in protein and organelle turnover. Cold Spring Harb. Symp. Quant. Biol. 2011, 76:397-402.
27. Mizushima N., Levine B. Autophagy in mammalian development and differentiation. Nat. Cell Biol. 2010, 12:823-830.
28. Nakatogawa H., Suzuki K., Kamada Y., Ohsumi Y. Dynamics and diversity in autophagy mechanisms: lessons from yeast. Nat. Rev. Mol. Cell Biol. 2009, 10:458-467.
29. Nakatogawa H., Ohbayashi S., Sakoh-Nakatogawa M., Kakuta S., Suzuki S.W., Kirisako H., Kondo-Kakuta C., Noda N.N., Yamamoto H., Ohsumi Y. The autophagy-related protein kinase Atg1 interacts with the ubiquitin-like protein Atg8 via the Atg8 family interacting motif to facilitate autophagosome formation. J. Biol. Chem. 2012, 287:28503-28507.
30. Nazio F., Strappazzon F., Antonioli M., Bielli P., Cianfanelli V., Bordi M., Gretzmeier C., Dengjel J., Piacentini M., Fimia G.M., Cecconi F. mTOR inhibits autophagy by controlling ULK1 ubiquitylation, self-association and function through AMBRA1 and TRAF6. Nat. Cell Biol. 2013, 15:406-416.
31. Neel B.A., Lin Y., Pessin J.E. Skeletal muscle autophagy: a new metabolic regulator. Trends Endocrinol. Metab. 2013, 24:635-643.
32. O Farrell F., Rusten T.E., Stenmark H. Phosphoinositide 3-kinases as accelerators and brakes of autophagy. FEBS J. 2013, 280:6322-6337.
33. Platta H.W., Abrahamsen H., Thoresen S.B., Stenmark H. Nedd4-dependent lysine-11-linked polyubiquitination of the tumour suppressor Beclin 1. Biochem. J. 2012, 441:399-406.
34. Proikas-Cezanne T., Takacs Z., Dönnes P., Kohlbacher O. WIPI proteins: essential PtdIns3P effectors at the nascent autophagosome. J. Cell Sci. 2015, 128:207-217.
35. Russell R.C., Tian Y., Yuan H., Park H.W., Chang Y.Y., Kim J., Kim H., Neufeld T.P., Dillin A., Guan K.L. ULK1 induces autophagy by phosphorylating Beclin-1 and activating VPS34 lipid kinase. Nat. Cell Biol. 2013, 15:741-750.
36. Sala D., Ivanova S., Plana N., Ribas V., Duran J., Bach D., Turkseven S., Laville M., Vidal H., Karczewska-Kupczewska M., et al. Autophagy-regulating TP53INP2 mediates muscle wasting and is repressed in diabetes. J. Clin. Invest. 2014, 124:1914-1927.
37. Sandri M., Coletto L., Grumati P., Bonaldo P. Misregulation of autophagy and protein degradation systems in myopathies and muscular dystrophies. J. Cell Sci. 2013, 126:5325-5333.
38. Schink K.O., Raiborg C., Stenmark H. Phosphatidylinositol 3-phosphate, a lipid that regulates membrane dynamics, protein sorting and cell signalling. BioEssays 2013, 35:900-912.
39. Schwander M., Leu M., Stumm M., Dorchies O.M., Ruegg U.T., Schittny J., Müller U. Beta1 integrins regulate myoblast fusion and sarcomere assembly. Dev. Cell 2003, 4:673-685.
40. Shi C.S., Kehrl J.H. TRAF6 and A20 regulate lysine 63-linked ubiquitination of Beclin-1 to control TLR4-induced autophagy. Sci. Signal. 2010, 3:ra42.
41. Sun Q., Fan W., Chen K., Ding X., Chen S., Zhong Q. Identification of Barkor as a mammalian autophagy-specific factor for Beclin 1 and class III phosphatidylinositol 3-kinase. Proc. Natl. Acad. Sci. USA 2008, 105:19211-19216.
42. Suttangkakul A., Li F., Chung T., Vierstra R.D. The ATG1/ATG13 protein kinase complex is both a regulator and a target of autophagic recycling in Arabidopsis. Plant Cell 2011, 23:3761-3779.
43. Thoresen S.B., Pedersen N.M., Liestøl K., Stenmark H. A phosphatidylinositol 3-kinase class III sub-complex containing VPS15, VPS34, Beclin 1, UVRAG and BIF-1 regulates cytokinesis and degradative endocytic traffic. Exp. Cell Res. 2010, 316:3368-3378.
44. Wirth M., Joachim J., Tooze S.A. Autophagosome formation--the role of ULK1 and Beclin1-PI3KC3 complexes in setting the stage. Semin. Cancer Biol. 2013, 23:301-309.
45. Wong P.M., Puente C., Ganley I.G., Jiang X. The ULK1 complex: sensing nutrient signals for autophagy activation. Autophagy 2013, 9:124-137.
46. Xia P., Wang S., Du Y., Zhao Z., Shi L., Sun L., Huang G., Ye B., Li C., Dai Z., et al. WASH inhibits autophagy through suppression of Beclin 1 ubiquitination. EMBO J. 2013, 32:2685-2696.
47. Xiao J., Zhang T., Xu D., Wang H., Cai Y., Jin T., Liu M., Jin M., Wu K., Yuan J. FBXL20-mediated Vps34 ubiquitination as a p53 controlled checkpoint in regulating autophagy and receptor degradation. Genes Dev. 2015, 29:184-196.
48. Xu C., Feng K., Zhao X., Huang S., Cheng Y., Qian L., Wang Y., Sun H., Jin M., Chuang T.H., Zhang Y. Regulation of autophagy by E3 ubiquitin ligase RNF216 through BECN1 ubiquitination. Autophagy 2014, 10:2239-2250.
49. Yang Z., Klionsky D.J. Mammalian autophagy: core molecular machinery and signaling regulation. Curr. Opin. Cell Biol. 2010, 22:124-131.
50. Yu L., McPhee C.K., Zheng L., Mardones G.A., Rong Y., Peng J., Mi N., Zhao Y., Liu Z., Wan F., et al. Termination of autophagy and reformation of lysosomes regulated by mTOR. Nature 2010, 465:942-946.
51. Zhang T., Dong K., Liang W., Xu D., Xia H., Geng J., Najafov A., Liu M., Li Y., Han X., et al. G-protein-coupled receptors regulate autophagy by ZBTB16-mediated ubiquitination and proteasomal degradation of Atg14L. eLife 2015, 4:e06734.