MEK1/2 overactivation can promote growth arrest by mediating ERK1/2-dependent phosphorylation of p70S6K

Journal of Cellular Physiology

Volumn 229, Issue 7, 2014, Pages 903-915

  Guégan, Jean Philippe ^a   Ezan, Frédéric ^a   Gailhouste, Luc ^a,b   Langouët, Sophie ^a   Baffet, Georges ^a  

^a UNIVERSITÉ DE RENNES 1   (France)

^b NATIONAL CANCER CENTER RESEARCH INSTITUTE   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; MITOGEN ACTIVATED PROTEIN KINASE KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE KINASE 2; P21 ACTIVATED KINASE; P70S6K PROTEIN; PROTEIN; UNCLASSIFIED DRUG;

ARTICLE; CELL CYCLE ARREST; CELL CYCLE PROGRESSION; CELL GROWTH; CELL PROLIFERATION; CELL STRAIN MCF 7; ENZYME ACTIVATION; ENZYME MECHANISM; G1 PHASE CELL CYCLE CHECKPOINT; GENE MUTATION; GENETIC TRANSCRIPTION; GROWTH DISORDER; HUMAN; HUMAN CELL; LIVER CELL CARCINOMA; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; PROTEIN PROCESSING; PROTEIN STABILITY; PROTEIN SYNTHESIS; TRANSIENT EXPRESSION;

CELL CYCLE CHECKPOINTS; CELL PROLIFERATION; CYCLIN-DEPENDENT KINASE INHIBITOR P21; G1 PHASE CELL CYCLE CHECKPOINTS; HEP G2 CELLS; HUMANS; MAP KINASE KINASE 1; MAP KINASE KINASE 2; MAP KINASE SIGNALING SYSTEM; PHOSPHORYLATION; PROTEIN BIOSYNTHESIS; RIBOSOMAL PROTEIN S6 KINASES, 70-KDA; RNA, SMALL INTERFERING; SIGNAL TRANSDUCTION;

EID: 84896530281     PISSN: 00219541     EISSN: 10974652     Source Type: Journal    
DOI: 10.1002/jcp.24521     Document Type: Article

References (73)

1. Belanger LF, Roy S, Tremblay M, Brott B, Steff AM, Mourad W, Hugo P, Erikson R, Charron J. 2003. Mek2 is dispensable for mouse growth and development. Mol Cell Biol 23:4778-4787.
2. Beuvink I, Boulay A, Fumagalli S, Zilbermann F, Ruetz S, O'Reilly T, Natt F, Hall J, Lane HA, Thomas G. 2005. The mTOR inhibitor RAD001 sensitizes tumor cells to DNA-damaged induced apoptosis through inhibition of p21 translation. Cell 120:747-759.
3. Brunet A, Pages G, Pouyssegur J. 1994. Constitutively active mutants of MAP kinase kinase (MEK1) induce growth factor-relaxation and oncogenicity when expressed in fibroblasts. Oncogene 9:3379-3387.
4. Bueno OF, De Windt LJ, Tymitz KM, Witt SA, Kimball TR, Klevitsky R, Hewett TE, Jones SP, Lefer DJ, Peng CF, Kitsis RN, Molkentin JD. 2000. The MEK1-ERK1/2 signaling pathway promotes compensated cardiac hypertrophy in transgenic mice. EMBO J 19:6341-6350.
5. Carriere A, Romeo Y, Acosta-Jaquez HA, Moreau J, Bonneil E, Thibault P, Fingar DC, Roux PP. 2011. ERK1/2 phosphorylate Raptor to promote Ras-dependent activation of mTOR complex 1 (mTORC1). J Biol Chem 286:567-577.
6. Chen D, Heath V, O'Garra A, Johnston J, McMahon M. 1999. Sustained activation of the raf-MEK-ERK pathway elicits cytokine unresponsiveness in T cells. J Immunol 163:5796-5805.
7. Child ES, Mann DJ. 2006. The intricacies of p21 phosphorylation: Protein/protein interactions, subcellular localization and stability. Cell Cycle 5:1313-1319.
8. Ciccarelli C, Marampon F, Scoglio A, Mauro A, Giacinti C, De Cesaris P, Zani B. 2005. p21WAF1 expression induced by MEK/ERK pathway activation or inhibition correlates with growth arrest, myogenic differentiation and onco-phenotype reversal in rhabdomyosarcoma cells. Mol Cancer 4:41.
9. Collado M, Gil J, Efeyan A, Guerra C, Schuhmacher AJ, Barradas M, Benguria A, Zaballos A, Flores JM, Barbacid M, Beach D, Serrano M. 2005. Tumour biology: Senescence in premalignant tumours. Nature 436:642.
10. Cowley S, Paterson H, Kemp P, Marshall CJ. 1994. Activation of MAP kinase kinase is necessary and sufficient for PC12 differentiation and for transformation of NIH 3T3 cells. Cell 77:841-852.
11. Eblen ST, Slack-Davis JK, Tarcsafalvi A, Parsons JT, Weber MJ, Catling AD. 2004. Mitogen-activated protein kinase feedback phosphorylation regulates MEK1 complex formation and activation during cellular adhesion. Mol Cell Biol 24:2308-2317.
12. Fenton TR, Gout IT. 2011. Functions and regulation of the 70kDa ribosomal S6 kinases. Int J Biochem Cell Biol 43:47-59.
13. Fremin C, Ezan F, Guegan JP, Gaillouste L, Trotard M, Seyec JL, Theret N, Langouet S, Baffet G. 2012. The complexity of ERK1 and ERK2 MAPKs in multiple hepatocyte fate responses. J Cell Physiol 227:59-69.
14. Frémin C, Bessard A, Ezan F, Gailhouste L, Régeard M, Le Seyec J, Gilot D, Pagès G, Pouysségur J, Langouët S, Baffet G. 2009. Multiple division cycles and long-term survival of hepatocytes are distinctly regulated by extracellular signal-regulated kinases ERK1 and ERK2. Hepatology 49:930-939.
15. Gaben AM, Saucier C, Bedin M, Barbu V, Mester J. 2004. Rapamycin inhibits cdk4 activation, p 21(WAF1/CIP1) expression and G1-phase progression in transformed mouse fibroblasts. Int J Cancer 108:200-206.
16. Gailhouste L, Ezan F, Bessard A, Fremin C, Rageul J, Langouet S, Baffet G. 2010. RNAi-mediated MEK1 knock-down prevents ERK1/2 activation and abolishes human hepatocarcinoma growth in vitro and in vivo. Int J Cancer 126:1367-1377.
17. Giroux S, Tremblay M, Bernard D, Cardin-Girard JF, Aubry S, Larouche L, Rousseau S, Huot J, Landry J, Jeannotte L, Charron J. 1999. Embryonic death of Mek1-deficient mice reveals a role for this kinase in angiogenesis in the labyrinthine region of the placenta. Curr Biol 9:369-372.
18. Gu M, Lynch J, Brecher P. 2000. Nitric oxide increases p21(Waf1/Cip1) expression by a cGMP-dependent pathway that includes activation of extracellular signal-regulated kinase and p70(S6k). J Biol Chem 275:11389-11396.
19. Guegan JP, Ezan F, Theret N, Langouet S, Baffet G. 2013. MAPK signaling in cisplatin-induced death: Predominant role of ERK1 over ERK2 in human hepatocellular carcinoma cells. Carcinogenesis 34:38-47.
20. Hong SK, Yoon S, Moelling C, Arthan D, Park JI. 2009. Noncatalytic function of ERK1/2 can promote Raf/MEK/ERK-mediated growth arrest signaling. J Biol Chem 284:33006-33018.
21. Iijima Y, Laser M, Shiraishi H, Willey CD, Sundaravadivel B, Xu L, McDermott PJ, Kuppuswamy D. 2002. c-Raf/MEK/ERK pathway controls protein kinase C-mediated p70S6K activation in adult cardiac muscle cells. J Biol Chem 277:23065-23075.
22. Kannan-Thulasiraman P, Dolniak B, Kaur S, Sassano A, Kalvakolanu DV, Hay N, Platanias LC. 2008. Role of the translational repressor 4E-BP1 in the regulation of p21(Waf1/Cip1) expression by retinoids. Biochem Biophys Res Commun 368:983-989.
23. Kim EK, Choi EJ. 2010. Pathological roles of MAPK signaling pathways in human diseases. Bioch Biophys Acta 1802:396-405.
24. Kim DH, Sarbassov DD, Ali SM, Latek RR, Guntur KV, Erdjument-Bromage H, Tempst P, Sabatini DM. 2003. GbetaL, a positive regulator of the rapamycin-sensitive pathway required for the nutrient-sensitive interaction between raptor and mTOR. Mol Cell 11:895-904.
25. Laser M, Kasi VS, Hamawaki M, Cooper Gt, Kerr CM, Kuppuswamy D. 1998. Differential activation of p70 and p85 S6 kinase isoforms during cardiac hypertrophy in the adult mammal. J Biol Chem 273:24610-24619.
26. Lee AW, Nambirajan S, Moffat JG. 1999. CSF-1 activates MAPK-dependent and p53-independent pathways to induce growth arrest of hormone-dependent human breast cancer cells. Oncogene 18:7477-7494.
27. Lee CS, Dykema KJ, Hawkins DM, Cherba DM, Webb CP, Furge KA, Duesbery NS. 2011. MEK2 is sufficient but not necessary for proliferation and anchorage-independent growth of SK-MEL-28 melanoma cells. PLoS ONE 6:e17165.
28. Lefloch R, Pouyssegur J, Lenormand P. 2007. Single and combined silencing of ERK1 and ERK2 reveals their positive contribution to growth signaling depending on their expression levels. Mol Cell Biol 28:511-527.
29. Lehman JA, Gomez-Cambronero J. 2002. Molecular crosstalk between p70S6k and MAPK cell signaling pathways. Biochem Biophys Res Commun 293:463-469.
30. Lehman JA, Calvo V, Gomez-Cambronero J. 2003. Mechanism of ribosomal p70S6 kinase activation by granulocyte macrophage colony-stimulating factor in neutrophils: Cooperation of a MEK-related, THR421/SER424 kinase and a rapamycin-sensitive, m-TOR-related THR389 kinase. J Biol Chem 278:28130-28138.
31. Lin AW, Barradas M, Stone JC, van Aelst L, Serrano M, Lowe SW. 1998. Premature senescence involving p53 and p16 is activated in response to constitutive MEK/MAPK mitogenic signaling. Genes Dev 12:3008-3019.
32. Ma L, Chen Z, Erdjument-Bromage H, Tempst P, Pandolfi PP. 2005. Phosphorylation and functional inactivation of TSC2 by Erk implications for tuberous sclerosis and cancer pathogenesis. Cell 121:179-193.
33. Magnuson B, Ekim B, Fingar DC. 2012. Regulation and function of ribosomal protein S6 kinase (S6K) within mTOR signalling networks. Biochem J 441:1-21.
34. Malumbres M, Barbacid M. 2003. RAS oncogenes: The first 30 years. Nat Rev Cancer 3:459-465.
35. Mamane Y, Petroulakis E, LeBacquer O, Sonenberg N. 2006. mTOR, translation initiation and cancer. Oncogene 25:6416-6422.
36. Michaloglou C, Vredeveld LC, Soengas MS, Denoyelle C, Kuilman T, van der Horst CM, Majoor DM, Shay JW, Mooi WJ, Peeper DS. 2005. BRAFE600-associated senescence-like cell cycle arrest of human naevi. Nature 436:720-724.
37. Miskimins WK, Wang G, Hawkinson M, Miskimins R. 2001. Control of cyclin-dependent kinase inhibitor p27 expression by cap-independent translation. Mol Cell Biol 21:4960-4967.
38. Murphy LO, Blenis J. 2006. MAPK signal specificity: The right place at the right time. Trends Biochem Sci 31:268-275.
39. Nadeau V, Guillemette S, Belanger LF, Jacob O, Roy S, Charron J. 2009. Map2k1 and Map2k2 genes contribute to the normal development of syncytiotrophoblasts during placentation. Development 136:1363-1374.
40. Norbury C, Blow J, Nurse P. 1991. Regulatory phosphorylation of the p34cdc2 protein kinase in vertebrates. EMBO J 10:3321-3329.
41. Olsen CL, Gardie B, Yaswen P, Stampfer MR. 2002. Raf-1-induced growth arrest in human mammary epithelial cells is p16-independent and is overcome in immortal cells during conversion. Oncogene 21:6328-6339.
42. Park JS, Qiao L, Gilfor D, Yang MY, Hylemon PB, Benz C, Darlington G, Firestone G, Fisher PB, Dent P. 2000. A role for both Ets and C/EBP transcription factors and mRNA stabilization in the MAPK-dependent increase in p21 (Cip-1/WAF1/mda6) protein levels in primary hepatocytes. Mol Biol Cell 11:2915-2932.
43. Park JI, Strock CJ, Ball DW, Nelkin BD. 2003. The Ras/Raf/MEK/extracellular signal-regulated kinase pathway induces autocrine-paracrine growth inhibition via the leukemia inhibitory factor/JAK/STAT pathway. Mol Cell Biol 23:543-554.
44. Pelech S. 2006. Dimerization in protein kinase signaling. J Biol 5:12.
45. Ravi RK, Weber E, McMahon M, Williams JR, Baylin S, Mal A, Harter ML, Dillehay LE, Claudio PP, Giordano A, Nelkin BD, Mabry M. 1998. Activated Raf-1 causes growth arrest in human small cell lung cancer cells. J Clin Invest 101:153-159.
46. Ray PS, Grover R, Das S. 2006. Two internal ribosome entry sites mediate the translation of p53 isoforms. EMBO Rep 7:404-410.
47. Salmond RJ, Emery J, Okkenhaug K, Zamoyska R. 2009. MAPK, phosphatidylinositol 3-kinase, and mammalian target of rapamycin pathways converge at the level of ribosomal protein S6 phosphorylation to control metabolic signaling in CD8 T cells. J Immunol 183:7388-7397.
48. 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 raptor-independent pathway that regulates the cytoskeleton. Curr Biol 14:1296-1302.
49. Schaeffer HJ, Catling AD, Eblen ST, Collier LS, Krauss A, Weber MJ. 1998. M P1: A MEK binding partner that enhances enzymatic activation of the MAP kinase cascade. Science 281:1668-1671.
50. Scholl FA, Dumesic PA, Khavari PA. 2004. Mek1 alters epidermal growth and differentiation. Cancer Res 64:6035-6040.
51. Scholl FA, Dumesic PA, Barragan DI, Harada K, Charron J, Khavari PA. 2009. Selective role for Mek1 but not Mek2 in the induction of epidermal neoplasia. Cancer Res 69:3772-3778.
52. Serrano M, Lin AW, McCurrach ME, Beach D, Lowe SW. 1997. Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell 88:593-602.
53. Sewing A, Wiseman B, Lloyd AC, Land H. 1997. High-intensity Raf signal causes cell cycle arrest mediated by p21Cip1. Mol Cell Biol 17:5588-5597.
54. Shama J, Garcia-Medina R, Pouysségur J, Vial E. 2008. Major contribution of MEK1 to the activation of ERK1/ERK2 and to the growth of LS174T colon carcinoma cells. Biochem Biophys Res Commun 372:845-849.
55. Shaul Y, Seger R. 2007. The MEK/ERK cascade: From signaling specificity to diverse functions. Biochim Biophys Acta-Molecul Cell Res 1773:1213-1226.
56. Shaul YD, Gibor G, Plotnikov A, Seger R. 2009. Specific phosphorylation and activation of ERK1c by MEK1b: A unique route in the ERK cascade. Genes Dev 23:1779-1790.
57. Shin S, Dimitri CA, Yoon S-O, Dowdle W, Blenis J. 2010. ERK2 but not ERK1 induces epithelial-to-mesenchymal transformation via DEF motif-dependent signaling events. Mol Cell 38:114-127.
58. Shiota G, Rhoads DB, Wang TC, Nakamura T, Schmidt EV. 1992. Hepatocyte growth factor inhibits growth of hepatocellular carcinoma cells. Proc Natl Acad Sci USA 89:373-377.
59. Shirako E, Hirayama N, Tsukada Y, Tanaka T, Kitamura N. 2008. Up-regulation of p21CIP1 expression mediated by ERK-dependent and -independent pathways contributes to hepatocyte growth factor-induced inhibition of HepG2 hepatoma cell proliferation. J Cell Biochem 104:176-188.
60. Sun P, Yoshizuka N, New L, Moser BA, Li Y, Liao R, Xie C, Chen J, Deng Q, Yamout M, Dong MQ, Frangou CG, Yates JR 3rd, Wright PE, Han J. 2007. PRAK is essential for ras-induced senescence and tumor suppression. Cell 128:295-308.
61. Tombes RM, Auer KL, Mikkelsen R, Valerie K, Wymann MP, Marshall CJ, McMahon M, Dent P. 1998. The mitogen-activated protein (MAP) kinase cascade can either stimulate or inhibit DNA synthesis in primary cultures of rat hepatocytes depending upon whether its activation is acute/phasic or chronic. Biochem J 330:1451-1460.
62. Tsukada Y, Miyazawa K, Kitamura N. 2001. High intensity ERK signal mediates hepatocyte growth factor-induced proliferation inhibition of the human hepatocellular carcinoma cell line HepG2. J Biol Chem 276:40968-40976.
63. Ussar S. 2004. MEK1 and MEK2, different regulators of the G1/S transition. J Biol Chem 279:43861-43869.
64. Vaque JP, Navascues J, Shiio Y, Laiho M, Ajenjo N, Mauleon I, Matallanas D, Crespo P, Leon J. 2005. Myc antagonizes Ras-mediated growth arrest in leukemia cells through the inhibition of the Ras-ERK-p21Cip1 pathway. J Biol Chem 280:1112-1122.
65. Voisin L, Julien C, Duhamel S, Gopalbhai K, Claveau I, Saba-El-Leil MK, Rodrigue-Gervais I, Gaboury L, Lamarre D, Basik M, Meloche S. 2008. Activation of MEK1 or MEK2 isoform is sufficient to fully transform intestinal epithelial cells and induce the formation of metastatic tumors. BMC Cancer 8:337.
66. Voisin L, Saba-El-Leil MK, Julien C, Fremin C, Meloche S. 2010. Genetic demonstration of a redundant role of extracellular signal-regulated kinase 1 (ERK1) and ERK2 mitogen-activated protein kinases in promoting fibroblast proliferation. Mol Cell Biol 30:2918-2932.
67. von Thun A, Birtwistle M, Kalna G, Grindlay J, Strachan D, Kolch W, von Kriegsheim A, Norman JC. 2012. ERK2 drives tumour cell migration in three-dimensional microenvironments by suppressing expression of Rab17 and liprin-beta2. J Cell Sci 125:1465-1477.
68. Woods D, Parry D, Cherwinski H, Bosch E, Lees E, McMahon M. 1997. Raf-induced proliferation or cell cycle arrest is determined by the level of Raf activity with arrest mediated by p21Cip1. Mol Cell Biol 17:5598-5611.
69. Wortzel I, Seger R. 2011. The ERK cascade: Distinct functions within various subcellular organelles. Genes Cancer 2:195-209.
70. Wu X, Noh SJ, Zhou G, Dixon JE, Guan KL. 1996. Selective activation of MEK1 but not MEK2 by A-Raf from epidermal growth factor-stimulated Hela cells. J Biol Chem 271:3265-3271.
71. Ye X, Zerlanko B, Kennedy A, Banumathy G, Zhang R, Adams PD. 2007. Downregulation of Wnt signaling is a trigger for formation of facultative heterochromatin and onset of cell senescence in primary human cells. Mol Cell 27:183-196.
72. Zhang Y, Dong Z, Nomura M, Zhong S, Chen N, Bode AM. 2001. Signal transduction pathways involved in phosphorylation and activation of p70S6K following exposure to UVA irradiation. J Biol Chem 276:20913-20923.
73. Zhu J, Woods D, McMahon M, Bishop JM. 1998. Senescence of human fibroblasts induced by oncogenic Raf. Genes Dev 12:2997-3007.