AMP-activated protein kinase induces p53 by phosphorylating MDMX and inhibiting its activity

Molecular and Cellular Biology

Volumn 34, Issue 2, 2014, Pages 148-157

  He, Guifen ^a   Zhang, Yi Wei ^a   Lee, Jun Ho ^a,f   Zeng, Shelya X ^a   Wang, Yunyuan V ^c   Luo, Zhijun ^d   Dong, X Charlie ^b   Viollet, Benoit ^e,g,h   Wahl, Geoffrey M ^c   Lu, Hua ^a  

^a TULANE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b INDIANA UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c SALK INSTITUTE FOR BIOLOGICAL STUDIES   (United States)

^d BOSTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^e INSTITUT COCHIN   (France)

^f Daejeon University   (South Korea)

^g CNRS   (France)

^h UNIVERSITÉ PARIS DESCARTES   (France)

Author keywords

[No Author keywords available]

Indexed keywords

HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; METFORMIN; PROTEIN 14 3 3; PROTEIN MDMX; PROTEIN P53; SALICYLIC ACID;

ANIMAL EXPERIMENT; ARTICLE; ENZYME ACTIVATION; FIBROBLAST; HUMAN; HUMAN CELL; IMMUNOPRECIPITATION; IN VITRO STUDY; METABOLIC STRESS; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; UBIQUITINATION;

EID: 84891382131     PISSN: 02707306     EISSN: 10985549     Source Type: Journal    
DOI: 10.1128/MCB.00670-13     Document Type: Article

References (73)

1. Belyi VA, Ak P, Markert E, Wang H, Hu W, Puzio-Kuter A, Levine AJ 2010. The origins and evolution of the p53 family of genes. Cold Spring Harb. Perspect. Biol. 2:a001198. http://dx.doi.org/10.1101/cshperspect.a001198.
2. Johnson TM, Meade K, Pathak N, Marques MR, Attardi LD. 2008. Knockin mice expressing a chimeric p53 protein reveal mechanistic differences in how p53 triggers apoptosis and senescence. Proc. Natl. Acad. Sci. U. S. A. 105:1215-1220. http://dx.doi.org/10.1073/pnas.0706764105.
3. Barak Y, Juven T, Haffner R, Oren M. 1993. mdm2 expression is induced by wild type p53 activity. EMBO J. 12:461-468.
4. Momand J, Zambetti GP, Olson DC, George D, Levine AJ. 1992. The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation. Cell 69:1237-1245. http://dx.doi.org/10.1016/0092-8674(92)90644-R.
5. Shvarts A, Steegenga WT, Riteco N, van Laar T, Dekker P, Bazuine M, van Ham RC, van der Houven van Oordt W, Hateboer G, van der Eb AJ, Jochemsen AG. 1996. MDMX: a novel p53-binding protein with some functional properties of MDM2. EMBO J. 15:5349-5357.
6. Huang L, Yan Z, Liao X, Li Y, Yang J, Wang ZG, Zuo Y, Kawai H, Shadfan M, Ganapathy S, Yuan ZM. 2011. The p53 inhibitors MDM2/MDMX complex is required for control of p53 activity in vivo. Proc. Natl. Acad. Sci. U. S. A. 108:12001-12006. http://dx.doi.org/10.1073/pnas.1102309108.
7. Kawai H, Lopez-Pajares V, Kim MM, Wiederschain D, Yuan ZM. 2007. RING domain-mediated interaction is a requirement for MDM2's E3 ligase activity. Cancer Res. 67:6026-6030. http://dx.doi.org/10.1158/0008-5472.CAN-07-1313.
8. Pant V, Xiong S, Iwakuma T, Quintas-Cardama A, Lozano G. 2011. Heterodimerization of Mdm2 and Mdm4 is critical for regulating p53 activity during embryogenesis but dispensable for p53 and Mdm2 stability. Proc. Natl. Acad. Sci. U. S. A. 108:11995-12000. http://dx.doi.org/10.1073/pnas.1102241108.
9. Poyurovsky MV, Priest C, Kentsis A, Borden KL, Pan ZQ, Pavletich N, Prives C. 2007. The Mdm2 RING domain C-terminus is required for supramolecular assembly and ubiquitin ligase activity. EMBO J. 26:90-101. http://dx.doi.org/10.1038/sj.emboj.7601465.
10. Uldrijan S, Pannekoek WJ, Vousden KH. 2007. An essential function of the extreme C-terminus of MDM2 can be provided by MDMX. EMBO J. 26:102-112. http://dx.doi.org/10.1038/sj.emboj.7601469.
11. Iwakuma T, Lozano G. 2003. MDM2, an introduction. Mol. Cancer Res. 1:993-1000. http://mcr.aacrjournals.org/content/1/14/993.
12. Oliner JD, Pietenpol JA, Thiagalingam S, Gyuris J, Kinzler KW, Vogelstein B. 1993. Oncoprotein MDM2 conceals the activation domain of tumour suppressor p53. Nature 362:857-860. http://dx.doi.org/10.1038/362857a0.
13. Francoz S, Froment P, Bogaerts S, De Clercq S, Maetens M, Doumont G, Bellefroid E, Marine JC. 2006. Mdm4 and Mdm2 cooperate to inhibit p53 activity in proliferating and quiescent cells in vivo. Proc. Natl. Acad. Sci. U. S. A. 103:3232-3237. http://dx.doi.org/10.1073/pnas.0508476103.
14. Grier JD, Xiong S, Elizondo-Fraire AC, Parant JM, Lozano G. 2006. Tissue-specific differences of p53 inhibition by Mdm2 and Mdm4. Mol. Cell. Biol. 26:192-198. http://dx.doi.org/10.1128/MCB.26.1.192-198.2006.
15. Hilliard S, Aboudehen K, Yao X, El-Dahr SS. 2011. Tight regulation of p53 activity by Mdm2 is required for ureteric bud growth and branching. Dev. Biol. 353:354-366. http://dx.doi.org/10.1016/j.ydbio.2011.03.017.
16. Xiong S, Van Pelt CS, Elizondo-Fraire AC, Fernandez-Garcia B, Lozano G. 2007. Loss of Mdm4 results in p53-dependent dilated cardiomyopathy. Circulation 115:2925-2930. http://dx.doi.org/10.1161/CIRCULATIONAHA.107.689901.
17. Kruse JP, Gu W. 2009. Modes of p53 regulation. Cell 137:609-622. http://dx.doi.org/10.1016/j.cell.2009.04.050.
18. Wade M, Wang YV, Wahl GM. 2010. The p53 orchestra: Mdm2 and Mdmx set the tone. Trends Cell Biol. 20:299-309. http://dx.doi.org/10.1016/j.tcb.2010.01.009.
19. LeBron C, Chen L, Gilkes DM, Chen J. 2006. Regulation of MDMX nuclear import and degradation by Chk2 and 14-3-3. EMBO J. 25:1196-1206. http://dx.doi.org/10.1038/sj.emboj.7601032.
20. Okamoto K, Kashima K, Pereg Y, Ishida M, Yamazaki S, Nota A, Teunisse A, Migliorini D, Kitabayashi I, Marine JC, Prives C, Shiloh Y, Jochemsen AG, Taya Y. 2005. DNA damage-induced phosphorylation of MdmX at serine 367 activates p53 by targeting MdmX for Mdm2-dependent degradation. Mol. Cell. Biol. 25:9608-9620. http://dx.doi.org/10.1128/MCB.25.21.9608-9620.2005.
21. Pereg Y, Lam S, Teunisse A, Biton S, Meulmeester E, Mittelman L, Buscemi G, Okamoto K, Taya Y, Shiloh Y, Jochemsen AG. 2006. Differential roles of ATM- and Chk2-mediated phosphorylations of Hdmx in response to DNA damage. Mol. Cell. Biol. 26:6819-6831. http://dx.doi.org/10.1128/MCB.00562-06.
22. Jin Y, Dai MS, Lu SZ, Xu Y, Luo Z, Zhao Y, Lu H. 2006. 14-3-3gamma binds to MDMX that is phosphorylated by UV-activated Chk1, resulting in p53 activation. EMBO J. 25:1207-1218. http://dx.doi.org/10.1038/sj.emboj.7601010.
23. Wang YV, Leblanc M, Wade M, Jochemsen AG, Wahl GM. 2009. Increased radioresistance and accelerated B cell lymphomas in mice with Mdmx mutations that prevent modifications by DNA-damage-activated kinases. Cancer Cell 16:33-43. http://dx.doi.org/10.1016/j.ccr.2009.05.008.
24. Chen L, Gilkes DM, Pan Y, Lane WS, Chen J. 2005. ATM and Chk2-dependent phosphorylation of MDMX contribute to p53 activation after DNA damage. EMBO J. 24:3411-3422. http://dx.doi.org/10.1038/sj.emboj.7600812.
25. Lee JH, Jin Y, He G, Zeng SX, Wang V, Wahl GM, Lu H. 2012. Hypoxia activates the tumor suppressor p53 by inducing ATR-Chk1 kinase cascade-mediated phosphorylation and consequent 14-3-3gamma inactivation of MDMX. J. Biol. Chem. 287:20898-20903. http://dx.doi.org/10.1074/jbc. M111.336875.
26. Honda R, Yasuda H. 1999. Association of p19(ARF) with Mdm2 inhibits ubiquitin ligase activity of Mdm2 for tumor suppressor p53. EMBO J. 18:22-27. http://dx.doi.org/10.1093/emboj/18.1.22.
27. Zhang Y, Xiong Y, Yarbrough WG. 1998. ARF promotes MDM2 degradation and stabilizes p53: ARF-INK4a locus deletion impairs both the Rb and p53 tumor suppression pathways. Cell 92:725-734. http://dx.doi.org/10.1016/S0092-8674(00)81401-4.
28. Dai MS, Shi D, Jin Y, Sun XX, Zhang Y, Grossman SR, Lu H. 2006. Regulation of the MDM2-p53 pathway by ribosomal protein L11 involves a post-ubiquitination mechanism. J. Biol. Chem. 281:24304-24313. http://dx.doi.org/10.1074/jbc. M602596200.
29. Lohrum MA, Ludwig RL, Kubbutat MH, Hanlon M, Vousden KH. 2003. Regulation of HDM2 activity by the ribosomal protein L11. Cancer Cell 3:577-587. http://dx.doi.org/10.1016/S1535-6108(03)00134-X.
30. Zhang Q, Xiao H, Chai SC, Hoang QQ, Lu H. 2011. Hydrophilic residues are crucial for ribosomal protein L11 (RPL11) interaction with zinc finger domain of MDM2 and p53 protein activation. J. Biol. Chem. 286:38264-38274. http://dx.doi.org/10.1074/jbc. M111.277012.
31. Zhang Y, Lu H. 2009. Signaling to p53: ribosomal proteins find their way. Cancer Cell 16:369-377. http://dx.doi.org/10.1016/j.ccr.2009.09.024.
32. Zhang Y, Wolf GW, Bhat K, Jin A, Allio T, Burkhart WA, Xiong Y. 2003. Ribosomal protein L11 negatively regulates oncoprotein MDM2 and mediates a p53-dependent ribosomal-stress checkpoint pathway. Mol. Cell. Biol. 23:8902-8912. http://dx.doi.org/10.1128/MCB.23.23.8902-8912.2003.
33. Gilkes DM, Chen L, Chen J. 2006. MDMX regulation of p53 response to ribosomal stress. EMBO J. 25:5614-5625. http://dx.doi.org/10.1038/sj.emboj.7601424.
34. Li M, Gu W. 2011. A critical role for noncoding 5S rRNA in regulating Mdmx stability. Mol. Cell 43:1023-1032. http://dx.doi.org/10.1016/j.molcel.2011.08.020.
35. Hawley SA, Boudeau J, Reid JL, Mustard KJ, Udd L, Makela TP, Alessi DR, Hardie DG. 2003. Complexes between the LKB1 tumor suppressor, STRAD alpha/beta and MO25 alpha/beta are upstream kinases in the AMP-activated protein kinase cascade. J. Biol. 2:28. http://dx.doi.org/10.1186/1475-4924-2-28.
36. Woods A, Johnstone SR, Dickerson K, Leiper FC, Fryer LG, Neumann D, Schlattner U, Wallimann T, Carlson M, Carling D. 2003. LKB1 is the upstream kinase in the AMP-activated protein kinase cascade. Curr. Biol. 13:2004-2008. http://dx.doi.org/10.1016/j.cub.2003.10.031.
37. Lee DH, Lee TH, Jung CH, Kim YH. 2012. Wogonin induces apoptosis by activating the AMPK and p53 signaling pathways in human glioblastoma cells. Cell. Signal. 24:2216-2225. http://dx.doi.org/10.1016/j.cellsig.2012.07.019.
38. Thoreen CC, Sabatini DM. 2005. AMPK and p53 help cells through lean times. Cell Metab. 1:287-288. http://dx.doi.org/10.1016/j.cmet.2005.04.009.
39. Jones RG, Plas DR, Kubek S, Buzzai M, Mu J, Xu Y, Birnbaum MJ, Thompson CB. 2005. AMP-activated protein kinase induces a p53-dependent metabolic checkpoint. Mol. Cell 18:283-293. http://dx.doi.org/10.1016/j.molcel.2005.03.027.
40. Ashcroft M, Kubbutat MH, Vousden KH. 1999. Regulation of p53 function and stability by phosphorylation. Mol. Cell. Biol. 19:1751-1758.
41. Chao C, Saito S, Anderson CW, Appella E, Xu Y. 2000. Phosphorylation of murine p53 at Ser-18 regulates the p53 responses toDNAdamage. Proc. Natl. Acad. Sci. U. S. A. 97:11936-11941. http://dx.doi.org/10.1073/pnas.220252297.
42. Laderoute KR, Amin K, Calaoagan JM, Knapp M, Le T, Orduna J, Foretz M, Viollet B. 2006. 5=-AMP-activated protein kinase (AMPK) is induced by low-oxygen and glucose deprivation conditions found in solid-tumor microenvironments. Mol. Cell. Biol. 26:5336-5347. http://dx.doi.org/10.1128/MCB.00166-06.
43. Zeng X, Chen L, Jost CA, Maya R, Keller D, Wang X, Kaelin WG, Jr, Oren M, Chen J, Lu H. 1999. MDM2 suppresses p73 function without promoting p73 degradation. Mol. Cell. Biol. 19:3257-3266.
44. Hawley SA, Fullerton MD, Ross FA, Schertzer JD, ChevtzoffC, Walker KJ, Peggie MW, Zibrova D, Green KA, Mustard KJ, Kemp BE, Sakamoto K, Steinberg GR, Hardie DG. 2012. The ancient drug salicylate directly activates AMP-activated protein kinase. Science 336:918-922. http://dx.doi.org/10.1126/science.1215327.
45. National Research Council. 2011. Guide for the care and use of laboratory animals, 8th ed. National Academies Press, Washington, DC.
46. Okoshi R, Ozaki T, Yamamoto H, Ando K, Koida N, Ono S, Koda T, Kamijo T, Nakagawara A, Kizaki H. 2008. Activation of AMP-activated protein kinase induces p53-dependent apoptotic cell death in response to energetic stress. J. Biol. Chem. 283:3979-3987. http://dx.doi.org/10.1074/jbc. M705232200.
47. Deisenroth C, Zhang Y. 2011. The ribosomal protein-Mdm2-p53 pathway and energy metabolism: bridging the gap between feast and famine. Genes Cancer 2:392-403. http://dx.doi.org/10.1177/1947601911409737.
48. Zhang F, Hamanaka RB, Bobrovnikova-Marjon E, Gordan JD, Dai MS, Lu H, Simon MC, Diehl JA. 2006. Ribosomal stress couples the unfolded protein response to p53-dependent cell cycle arrest. J. Biol. Chem. 281: 30036-30045. http://dx.doi.org/10.1074/jbc. M604674200.
49. Mentzer RM, Jr, Ely SW, Lasley RD, Berne RM. 1988. The acute effects of AICAR on purine nucleotide metabolism and postischemic cardiac function. J. Thorac. Cardiovasc. Surg. 95:286-293.
50. Maclaine NJ, Hupp TR. 2009. The regulation of p53 by phosphorylation: a model for how distinct signals integrate into the p53 pathway. Aging (Albany NY) 1:490-502. http://www.impactaging.com/papers/v1/n5/full/100047.html.
51. Witters LA, Nordlund AC, Marshall L. 1991. Regulation of intracellular acetyl-CoA carboxylase by ATP depletors mimics the action of the 5=-AMP-activated protein kinase. Biochem. Biophys. Res. Commun. 181: 1486-1492. http://dx.doi.org/10.1016/0006-291X(91)92107-U.
52. Cool B, Zinker B, Chiou W, Kifle L, Cao N, Perham M, Dickinson R, Adler A, Gagne G, Iyengar R, Zhao G, Marsh K, Kym P, Jung P, Camp HS, Frevert E. 2006. Identification and characterization of a small moleculeAMPKactivator that treats key components of type 2 diabetes and the metabolic syndrome. Cell Metab. 3:403-416. http://dx.doi.org/10.1016/j.cmet.2006.05.005.
53. Yu LF, Qiu BY, Nan FJ, Li J. 2010. AMPK activators as novel therapeutics for type 2 diabetes. Curr. Top. Med. Chem. 10:397-410. http://dx.doi.org/10.2174/156802610790980611.
54. Zhang BB, Zhou G, Li C. 2009. AMPK: an emerging drug target for diabetes and the metabolic syndrome. Cell Metab. 9:407-416. http://dx.doi.org/10.1016/j.cmet.2009.03.012.
55. Zhang Y, Wang Y, Bao C, Xu Y, Shen H, Chen J, Yan J, Chen Y. 2012. Metformin interacts with AMPK through binding to gamma subunit. Mol. Cell. Biochem. 368:69-76. http://dx.doi.org/10.1007/s11010-012-1344-5.
56. Zhou G, Myers R, Li Y, Chen Y, Shen X, Fenyk-Melody J, Wu M, Ventre J, Doebber T, Fujii N, Musi N, Hirshman MF, Goodyear LJ, Moller DE. 2001. Role of AMP-activated protein kinase in mechanism of metformin action. J. Clin. Invest. 108:1167-1174. http://dx.doi.org/10.1172/JCI13505.
57. Karnevi E, Said K, Andersson R, Rosendahl AH. 2013. Metforminmediated growth inhibition involves suppression of the IGF-I receptor signalling pathway in human pancreatic cancer cells. BMC Cancer 13:235. http://dx.doi.org/10.1186/1471-2407-13-235.
58. Sarfstein R, Friedman Y, Attias-Geva Z, Fishman A, Bruchim I, Werner H. 2013. Metformin downregulates the insulin/IGF-I signaling pathway and inhibits different uterine serous carcinoma (USC) cells proliferation and migration in p53-dependent or -independent manners. PLoS One 8:e61537. http://dx.doi.org/10.1371/journal.pone.0061537.
59. Wang S, Song P, Zou MH. 2012. Inhibition of AMP-activated protein kinase alpha (AMPKalpha) by doxorubicin accentuates genotoxic stress and cell death in mouse embryonic fibroblasts and cardiomyocytes: role of p53 and SIRT1. J. Biol. Chem. 287:8001-8012. http://dx.doi.org/10.1074/jbc. M111.315812.
60. Lee SK, Lee JO, Kim JH, Kim SJ, You GY, Moon JW, Jung JH, Park SH, Uhm KO, Park JM, Suh PG, Kim HS. 2011. Metformin sensitizes insulin signaling through AMPK-mediated PTEN down-regulation in preadi-pocyte 3T3-L1 cells. J. Cell. Biochem. 112:1259-1267. http://dx.doi.org/10.1002/jcb.23000.
61. Ou HY, Cheng JT, Yu EH, Wu TJ. 2006. Metformin increases insulin sensitivity and plasma beta-endorphin in human subjects. Horm. Metab. Res. 38:106-111. http://dx.doi.org/10.1055/s-2006-925128.
62. Palomba S, Falbo A, Russo T, Manguso F, Tolino A, Zullo F, De Feo P, Orio F, Jr. 2007. Insulin sensitivity after metformin suspension in normal-weight women with polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 92:3128-3135. http://dx.doi.org/10.1210/jc.2007-0441.
63. Ben Sahra I, Laurent K, Giuliano S, Larbret F, Ponzio G, Gounon P, Le Marchand-Brustel Y, Giorgetti-Peraldi S, Cormont M, Bertolotto C, Deckert M, Auberger P, Tanti JF, Bost F. 2010. Targeting cancer cell metabolism: the combination of metformin and 2-deoxyglucose induces p53-dependent apoptosis in prostate cancer cells. Cancer Res. 70:2465-2475. http://dx.doi.org/10.1158/0008-5472.CAN-09-2782.
64. Storozhuk Y, Hopmans SN, Sanli T, Barron C, Tsiani E, Cutz JC, Pond G, Wright J, Singh G, Tsakiridis T. 2013. Metformin inhibits growth and enhances radiation response of non-small cell lung cancer (NSCLC) through ATM and AMPK. Br. J. Cancer 108:2021-2032. http://dx.doi.org/10.1038/bjc.2013.187.
65. Ben Sahra I, Regazzetti C, Robert G, Laurent K, Le Marchand-Brustel Y, Auberger P, Tanti JF, Giorgetti-Peraldi S, Bost F. 2011. Metformin, independent of AMPK, induces mTOR inhibition and cell-cycle arrest through REDD1. Cancer Res. 71:4366-4372. http://dx.doi.org/10.1158/0008-5472.CAN-10-1769.
66. Janjetovic K, Harhaji-Trajkovic L, Misirkic-Marjanovic M, Vucicevic L, Stevanovic D, Zogovic N, Sumarac-Dumanovic M, Micic D, Trajkovic V. 2011. In vitro and in vivo anti-melanoma action of metformin. Eur. J. Pharmacol. 668:373-382. http://dx.doi.org/10.1016/j.ejphar.2011.07.004.
67. Ekinci D, Senturk M, Kufrevioglu OI. 2011. Salicylic acid derivatives: synthesis, features and usage as therapeutic tools. Expert Opin. Ther. Pat. 21:1831-1841. http://dx.doi.org/10.1517/13543776.2011.636354.
68. Higgs GA, Salmon JA, Henderson B, Vane JR. 1987. Pharmacokinetics of aspirin and salicylate in relation to inhibition of arachidonate cyclooxygenase and antiinflammatory activity. Proc. Natl. Acad. Sci. U. S. A. 84: 1417-1420. http://dx.doi.org/10.1073/pnas.84.5.1417.
69. Fleischman A, Shoelson SE, Bernier R, Goldfine AB. 2008. Salsalate improves glycemia and inflammatory parameters in obese young adults. Diabetes Care 31:289-294. http://dx.doi.org/10.2337/dc07-1338.
70. Goldfine AB, Fonseca V, Jablonski KA, Pyle L, Staten MA, Shoelson SE. 2010. The effects of salsalate on glycemic control in patients with type 2 diabetes: a randomized trial. Ann. Intern. Med. 152:346-357. http://dx.doi.org/10.7326/0003-4819-152-6-201003160-00004.
71. Elwood PC, Gallagher AM, Duthie GG, Mur LA, Morgan G. 2009. Aspirin, salicylates, and cancer. Lancet 373:1301-1309. http://dx.doi.org/10.1016/S0140-6736(09)60243-9.
72. Hardie DG, Scott JW, Pan DA, Hudson ER. 2003. Management of cellular energy by the AMP-activated protein kinase system. FEBS Lett. 546:113-120. http://dx.doi.org/10.1016/S0014-5793(03)00560-X.
73. Suter M, Riek U, Tuerk R, Schlattner U, Wallimann T, Neumann D. 2006. Dissecting the role of 5'-AMP for allosteric stimulation, activation, and deactivation of AMP-activated protein kinase. J. Biol. Chem. 281: 32207-32216. http://dx.doi.org/10.1074/jbc. M606357200.