Phosphorylation of p62 Activates the Keap1-Nrf2 Pathway during Selective Autophagy

Molecular Cell

Volumn 51, Issue 5, 2013, Pages 618-631

  Ichimura, Yoshinobu ^a   Waguri, Satoshi ^b   Sou, Yu shin ^a   Kageyama, Shun ^a   Hasegawa, Jun ^a   Ishimura, Ryosuke ^a   Saito, Tetsuya ^a   Yang, Yinjie ^a   Kouno, Tsuguka ^a   Fukutomi, Toshiaki ^c   Hoshii, Takayuki ^d   Hirao, Atsushi ^d   Takagi, Kenji ^e   Mizushima, Tsunehiro ^e   Motohashi, Hozumi ^c   Lee, Myung Shik ^f   Yoshimori, Tamotsu ^g   Tanaka, Keiji ^a   Yamamoto, Masayuki ^c   Komatsu, Masaaki ^a  

^a TOKYO METROPOLITAN INSTITUTE OF MEDICAL SCIENCE   (Japan)

^b FUKUSHIMA MEDICAL UNIVERSITY   (Japan)

^c TOHOKU UNIVERSITY GRADUATE SCHOOL OF MEDICINE   (Japan)

^d KANAZAWA UNIVERSITY   (Japan)

^e UNIVERSITY OF HYOGO   (Japan)

^f Samsung Medical Center   (South Korea)

^g OSAKA UNIVERSITY GRADUATE SCHOOL OF MEDICINE   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

KELCH LIKE ECH ASSOCIATED PROTEIN 1; PROTEIN P62; TRANSCRIPTION FACTOR NRF2;

ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; AUTOPHAGY; HUMAN; HUMAN CELL; HUMAN TISSUE; LIVER CELL CARCINOMA; MOUSE; NONHUMAN; PROTEIN ANALYSIS; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION;

ADAPTOR PROTEINS, SIGNAL TRANSDUCING; ADENOMA; AMINO ACID SEQUENCE; ANIMALS; AUTOPHAGY; CARCINOMA, HEPATOCELLULAR; CRYSTALLOGRAPHY, X-RAY; CYTOSKELETAL PROTEINS; HEAT-SHOCK PROTEINS; LIVER NEOPLASMS; MICE; MOLECULAR SEQUENCE DATA; MULTIPROTEIN COMPLEXES; NF-E2-RELATED FACTOR 2; PHOSPHORYLATION; RNA-BINDING PROTEINS; TOR SERINE-THREONINE KINASES;

EID: 84883830467     PISSN: 10972765     EISSN: 10974164     Source Type: Journal    
DOI: 10.1016/j.molcel.2013.08.003     Document Type: Article

References (49)

1. Bae S.H., Sung S.H., Oh S.Y., Lim J.M., Lee S.K., Park Y.N., Lee H.E., Kang D., Rhee S.G. Sestrins activate Nrf2 by promoting p62-dependent autophagic degradation of Keap1 and prevent oxidative liver damage. Cell Metab. 2013, 17:73-84.
2. Bedford L., Hay D., Devoy A., Paine S., Powe D.G., Seth R., Gray T., Topham I., Fone K., Rezvani N., et al. Depletion of 26S proteasomes in mouse brain neurons causes neurodegeneration and Lewy-like inclusions resembling human pale bodies. J.Neurosci. 2008, 28:8189-8198.
3. Bjørkøy G., Lamark T., Brech A., Outzen H., Perander M., Overvatn A., Stenmark H., Johansen T. p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death. J.Cell Biol. 2005, 171:603-614.
4. DeNicola G.M., Karreth F.A., Humpton T.J., Gopinathan A., Wei C., Frese K., Mangal D., Yu K.H., Yeo C.J., Calhoun E.S., et al. Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis. Nature 2011, 475:106-109.
5. Deretic V., Levine B. Autophagy, immunity, and microbial adaptations. Cell Host Microbe 2009, 5:527-549.
6. Dupont N., Lacas-Gervais S., Bertout J., Paz I., Freche B., Van Nhieu G.T., van der Goot F.G., Sansonetti P.J., Lafont F. Shigella phagocytic vacuolar membrane remnants participate in the cellular response to pathogen invasion and are regulated by autophagy. Cell Host Microbe 2009, 6:137-149.
7. Duran A., Linares J.F., Galvez A.S., Wikenheiser K., Flores J.M., Diaz-Meco M.T., Moscat J. The signaling adaptor p62 is an important NF-kappaB mediator in tumorigenesis. Cancer Cell 2008, 13:343-354.
8. Duran A., Amanchy R., Linares J.F., Joshi J., Abu-Baker S., Porollo A., Hansen M., Moscat J., Diaz-Meco M.T. p62 is a key regulator of nutrient sensing in the mTORC1 pathway. Mol. Cell 2011, 44:134-146.
9. Emsley P., Cowtan K. Coot: model-building tools for molecular graphics. Acta Crystallogr. D Biol. Crystallogr. 2004, 60:2126-2132.
10. Geisler S., Holmström K.M., Skujat D., Fiesel F.C., Rothfuss O.C., Kahle P.J., Springer W. PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1. Nat. Cell Biol. 2010, 12:119-131.
11. Hayes J.D., McMahon M. NRF2 and KEAP1 mutations: permanent activation of an adaptive response in cancer. Trends Biochem. Sci. 2009, 34:176-188.
12. Hoshii T., Tadokoro Y., Naka K., Ooshio T., Muraguchi T., Sugiyama N., Soga T., Araki K., Yamamura K., Hirao A. mTORC1 is essential for leukemia propagation but not stem cell self-renewal. J.Clin. Invest. 2012, 122:2114-2129.
13. 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.
14. Inami Y., Waguri S., Sakamoto A., Kouno T., Nakada K., Hino O., Watanabe S., Ando J., Iwadate M., Yamamoto M., et al. Persistent activation of Nrf2 through p62 in hepatocellular carcinoma cells. J.Cell Biol. 2011, 193:275-284.
15. Itakura E., Mizushima N. p62 Targeting to the autophagosome formation site requires self-oligomerization but not LC3 binding. J.Cell Biol. 2011, 192:17-27.
16. Jain A., Lamark T., Sjøttem E., Larsen K.B., Awuh J.A., Øvervatn A., McMahon M., Hayes J.D., Johansen T. p62/SQSTM1 is a target gene for transcription factor NRF2 and creates a positive feedback loop by inducing antioxidant response element-driven gene transcription. J.Biol. Chem. 2010, 285:22576-22591.
17. Johansen T., Lamark T. Selective autophagy mediated by autophagic adapter proteins. Autophagy 2011, 7:279-296.
18. Kensler T.W., Wakabayashi N., Biswal S. Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway. Annu. Rev. Pharmacol. Toxicol. 2007, 47:89-116.
19. Kirkin V., McEwan D.G., Novak I., Dikic I. A role for ubiquitin in selective autophagy. Mol. Cell 2009, 34:259-269.
20. Kobayashi S., Kojidani T., Osakada H., Yamamoto A., Yoshimori T., Hiraoka Y., Haraguchi T. Artificial induction of autophagy around polystyrene beads in nonphagocytic cells. Autophagy 2010, 6:36-45.
21. Komatsu M., Waguri S., Koike M., Sou Y.S., Ueno T., Hara T., Mizushima N., Iwata J., Ezaki J., Murata S., et al. Homeostatic levels of p62 control cytoplasmic inclusion body formation in autophagy-deficient mice. Cell 2007, 131:1149-1163.
22. Komatsu M., Kurokawa H., Waguri S., Taguchi K., Kobayashi A., Ichimura Y., Sou Y.S., Ueno I., Sakamoto A., Tong K.I., et al. The selective autophagy substrate p62 activates the stress responsive transcription factor Nrf2 through inactivation of Keap1. Nat. Cell Biol. 2010, 12:213-223.
23. Kroemer G., Mariño G., Levine B. Autophagy and the integrated stress response. Mol. Cell 2010, 40:280-293.
24. Lau A., Wang X.J., Zhao F., Villeneuve N.F., Wu T., Jiang T., Sun Z., White E., Zhang D.D. A noncanonical mechanism of Nrf2 activation by autophagy deficiency: direct interaction between Keap1 and p62. Mol. Cell. Biol. 2010, 30:3275-3285.
25. Ling J., Kang Y., Zhao R., Xia Q., Lee D.F., Chang Z., Li J., Peng B., Fleming J.B., Wang H., et al. KrasG12D-induced IKK2/β/NF-κB activation by IL-1α and p62 feedforward loops is required for development of pancreatic ductal adenocarcinoma. Cancer Cell 2012, 21:105-120.
26. Matsumoto G., Wada K., Okuno M., Kurosawa M., Nukina N. Serine 403 phosphorylation of p62/SQSTM1 regulates selective autophagic clearance of ubiquitinated proteins. Mol. Cell 2011, 44:279-289.
27. McAlpine F., Williamson L.E., Tooze S.A., Chan E.Y. Regulation of nutrient-sensitive autophagy by uncoordinated 51-like kinases 1 and 2. Autophagy 2013, 9:361-373.
28. Mitsuishi Y., Taguchi K., Kawatani Y., Shibata T., Nukiwa T., Aburatani H., Yamamoto M., Motohashi H. Nrf2 redirects glucose and glutamine into anabolic pathways in metabolic reprogramming. Cancer Cell 2012, 22:66-79.
29. Mizushima N., Levine B., Cuervo A.M., Klionsky D.J. Autophagy fights disease through cellular self-digestion. Nature 2008, 451:1069-1075.
30. Murshudov G.N., Vagin A.A., Dodson E.J. Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr. DBiol. Crystallogr. 1997, 53:240-255.
31. Narendra D., Kane L.A., Hauser D.N., Fearnley I.M., Youle R.J. p62/SQSTM1 is required for Parkin-induced mitochondrial clustering but not mitophagy; VDAC1 is dispensable for both. Autophagy 2010, 6:1090-1106.
32. Ooi A., Wong J.C., Petillo D., Roossien D., Perrier-Trudova V., Whitten D., Min B.W., Tan M.H., Zhang Z., Yang X.J., et al. An antioxidant response phenotype shared between hereditary and sporadic type 2 papillary renal cell carcinoma. Cancer Cell 2011, 20:511-523.
33. Otwinowski Z., Minor W. Processing of X-ray diffraction data collected in oscillation mode. Methods in Enzymology, Vol. 276: Macromolecular Crystallography, Pt. A 1997, 307-326. Academic Press, New York. J.N. Abelson, M.I. Simon, C.W. Carter, R.M. Sweet (Eds.).
34. Padmanabhan B., Tong K.I., Ohta T., Nakamura Y., Scharlock M., Ohtsuji M., Kang M.I., Kobayashi A., Yokoyama S., Yamamoto M. Structural basis for defects of Keap1 activity provoked by its point mutations in lung cancer. Mol. Cell 2006, 21:689-700.
35. Pilli M., Arko-Mensah J., Ponpuak M., Roberts E., Master S., Mandell M.A., Dupont N., Ornatowski W., Jiang S., Bradfute S.B., et al. TBK-1 promotes autophagy-mediated antimicrobial defense by controlling autophagosome maturation. Immunity 2012, 37:223-234.
36. Rubinsztein D.C., Mariño G., Kroemer G. Autophagy and aging. Cell 2011, 146:682-695.
37. Shibata T., Ohta T., Tong K.I., Kokubu A., Odogawa R., Tsuta K., Asamura H., Yamamoto M., Hirohashi S. Cancer related mutations in NRF2 impair its recognition by Keap1-Cul3 E3 ligase and promote malignancy. Proc. Natl. Acad. Sci. USA 2008, 105:13568-13573.
38. Sporn M.B., Liby K.T. NRF2 and cancer: the good, the bad and the importance of context. Nat. Rev. Cancer 2012, 12:564-571.
39. Taguchi K., Motohashi H., Yamamoto M. Molecular mechanisms of the Keap1-Nrf2 pathway in stress response and cancer evolution. Genes Cells 2011, 16:123-140.
40. Taguchi K., Fujikawa N., Komatsu M., Ishii T., Unno M., Akaike T., Motohashi H., Yamamoto M. Keap1 degradation by autophagy for the maintenance of redox homeostasis. Proc. Natl. Acad. Sci. USA 2012, 109:13561-13566.
41. Takamura A., Komatsu M., Hara T., Sakamoto A., Kishi C., Waguri S., Eishi Y., Hino O., Tanaka K., Mizushima N. Autophagy-deficient mice develop multiple liver tumors. Genes Dev. 2011, 25:795-800.
42. Tatsumi K., Yamamoto-Mukai H., Shimizu R., Waguri S., Sou Y.S., Sakamoto A., Taya C., Shitara H., Hara T., Chung C.H., et al. The Ufm1-activating enzyme Uba5 is indispensable for erythroid differentiation in mice. Nat Commun 2011, 2:181.
43. Vagin A., Teplyakov A. Molecular replacement with MOLREP. Acta Crystallogr. D Biol. Crystallogr. 2010, 66:22-25.
44. Villeneuve N.F., Lau A., Zhang D.D. Regulation of the Nrf2-Keap1 antioxidant response by the ubiquitin proteasome system: an insight into cullin-ring ubiquitin ligases. Antioxid. Redox Signal. 2010, 13:1699-1712.
45. Weidberg H., Shvets E., Elazar Z. Biogenesis and cargo selectivity of autophagosomes. Annu. Rev. Biochem. 2011, 80:125-156.
46. White E. Deconvoluting the context-dependent role for autophagy in cancer. Nat. Rev. Cancer 2012, 12:401-410.
47. Youle R.J., Narendra D.P. Mechanisms of mitophagy. Nat. Rev. Mol. Cell Biol. 2011, 12:9-14.
48. Zatloukal K., Stumptner C., Fuchsbichler A., Heid H., Schnoelzer M., Kenner L., Kleinert R., Prinz M., Aguzzi A., Denk H. p62 Is a common component of cytoplasmic inclusions in protein aggregation diseases. Am. J. Pathol. 2002, 160:255-263.
49. Zheng Y.T., Shahnazari S., Brech A., Lamark T., Johansen T., Brumell J.H. The adaptor protein p62/SQSTM1 targets invading bacteria to the autophagy pathway. J.Immunol. 2009, 183:5909-5916.