A Mortalin/HSPA9-Mediated Switch in Tumor-Suppressive Signaling of Raf/MEK/Extracellular Signal-Regulated Kinase

REFERENCES

• Shaul YD, Seger R. 2007. The MEK/ERK cascade: from signaling specificity to diverse functions. Biochim. Biophys. Acta 1773:1213–1226.
   PubMed Web of Science ®Google Scholar
• McCubrey JA, Steelman LS, Chappell WH, Abrams SL, Wong EW, Chang F, Lehmann B, Terrian DM, Milella M, Tafuri A, Stivala F, Libra M, Basecke J, Evangelisti C, Martelli AM, Franklin RA. 2007. Roles of the Raf/MEK/ERK pathway in cell growth, malignant transformation and drug resistance. Biochim. Biophys. Acta 1773:1263–1284.
   PubMed Web of Science ®Google Scholar
• Roberts PJ, Der CJ. 2007. Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer. Oncogene 26:3291–3310.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Zhu J, Woods D, McMahon M, Bishop JM. 1998. Senescence of human fibroblasts induced by oncogenic Raf. Genes Dev. 12:2997–3007.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Braig M, Lee S, Loddenkemper C, Rudolph C, Peters AH, Schlegelberger B, Stein H, Dorken B, Jenuwein T, Schmitt CA. 2005. Oncogene-induced senescence as an initial barrier in lymphoma development. Nature 436:660–665.
   PubMed Web of Science ®Google Scholar
• Mooi WJ, Peeper DS. 2006. Oncogene-induced cell senescence—halting on the road to cancer. N. Engl. J. Med. 355:1037–1046.
   PubMed Web of Science ®Google Scholar
• Courtois-Cox S, Jones SL, Cichowski K. 2008. Many roads lead to oncogene-induced senescence. Oncogene 27:2801–2809.
   PubMedGoogle Scholar
• McDuff FK, Turner SD. 2011. Jailbreak: oncogene-induced senescence and its evasion. Cell. Signal. 23:6–13.
   PubMedGoogle Scholar
• Daugaard M, Rohde M, Jaattela M. 2007. The heat shock protein 70 family: highly homologous proteins with overlapping and distinct functions. FEBS Lett. 581:3702–3710.
   PubMed Web of Science ®Google Scholar
• Deocaris CC, Widodo N, Ishii T, Kaul SC, Wadhwa R. 2007. Functional significance of minor structural and expression changes in stress chaperone mortalin. Ann. N. Y. Acad. Sci. 1119:165–175.
   PubMedGoogle Scholar
• Kaul SC, Deocaris CC, Wadhwa R. 2007. Three faces of mortalin: a housekeeper, guardian and killer. Exp. Gerontol. 42:263–274.
   PubMed Web of Science ®Google Scholar
• Wadhwa R, Takano S, Kaur K, Deocaris CC, Pereira-Smith OM, Reddel RR, Kaul SC. 2006. Upregulation of mortalin/mthsp70/Grp75 contributes to human carcinogenesis. Int. J. Cancer 118:2973–2980.
   PubMed Web of Science ®Google Scholar
• Wadhwa R, Takano S, Taira K, Kaul SC. 2004. Reduction in mortalin level by its antisense expression causes senescence-like growth arrest in human immortalized cells. J. Gene Med. 6:439–444.
   PubMedGoogle Scholar
• Wadhwa R, Takano S, Kaur K, Aida S, Yaguchi T, Kaul Z, Hirano T, Taira K, Kaul SC. 2005. Identification and characterization of molecular interactions between mortalin/mtHsp70 and HSP60. Biochem. J. 391:185–190.
   PubMedGoogle Scholar
• Wadhwa R, Takano S, Robert M, Yoshida A, Nomura H, Reddel RR, Mitsui Y, Kaul SC. 1998. Inactivation of tumor suppressor p53 by mot-2, a hsp70 family member. J. Biol. Chem. 273:29586–29591.
   PubMed Web of Science ®Google Scholar
• Wadhwa R, Yaguchi T, Hasan MK, Taira K, Kaul SC. 2003. Mortalin-MPD (mevalonate pyrophosphate decarboxylase) interactions and their role in control of cellular proliferation. Biochem. Biophys. Res. Commun. 302:735–742.
   PubMed Web of Science ®Google Scholar
• Lu WJ, Lee NP, Kaul SC, Lan F, Poon RT, Wadhwa R, Luk JM. 2011. Mortalin-p53 interaction in cancer cells is stress dependent and constitutes a selective target for cancer therapy. Cell Death Differ. 18:1046–1056.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMedGoogle Scholar
• Samuels ML, Weber MJ, Bishop JM, McMahon M. 1993. Conditional transformation of cells and rapid activation of the mitogen-activated protein kinase cascade by an estradiol-dependent human Raf-1 protein kinase. Mol. Cell. Biol. 13:6241–6252.
   PubMedGoogle Scholar
• Vindelov LL, Christensen IJ, Nissen NI. 1983. A detergent-trypsin method for the preparation of nuclei for flow cytometric DNA analysis. Cytometry 3:323–327.
   PubMedGoogle Scholar
• Mostoslavsky G, Fabian AJ, Rooney S, Alt FW, Mulligan RC. 2006. Complete correction of murine Artemis immunodeficiency by lentiviral vector-mediated gene transfer. Proc. Natl. Acad. Sci. U. S. A. 103:16406–16411.
   PubMed Web of Science ®Google Scholar
• Rubinson DA, Dillon CP, Kwiatkowski AV, Sievers C, Yang L, Kopinja J, Rooney DL, Zhang M, Ihrig MM, McManus MT, Gertler FB, Scott ML, Van Parijs L. 2003. A lentivirus-based system to functionally silence genes in primary mammalian cells, stem cells and transgenic mice by RNA interference. Nat. Genet. 33:401–406.
   PubMed Web of Science ®Google Scholar
• Beier F, Taylor AC, LuValle P. 1999. The Raf-1/MEK/ERK pathway regulates the expression of the p21Cip1/Waf1 gene in chondrocytes. J. Biol. Chem. 274:30273–30279.
   PubMed Web of Science ®Google Scholar
• Livak KJ, Schmittgen TD. 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method. Methods 25:402–408.
   PubMed Web of Science ®Google Scholar
• Hong SK, Kim JH, Lin MF, Park JI. 2011. The Raf/MEK/extracellular signal-regulated kinase 1/2 pathway can mediate growth inhibitory and differentiation signaling via androgen receptor downregulation in prostate cancer cells. Exp. Cell Res. 317:2671–2682.
   PubMedGoogle Scholar
• Bunz F, Dutriaux A, Lengauer C, Waldman T, Zhou S, Brown JP, Sedivy JM, Kinzler KW, Vogelstein B. 1998. Requirement for p53 and p21 to sustain G2 arrest after DNA damage. Science 282:1497–1501.
   PubMed Web of Science ®Google Scholar
• Abbas T, Dutta A. 2009. p21 in cancer: intricate networks and multiple activities. Nat. Rev. Cancer 9:400–414.
   PubMed Web of Science ®Google Scholar
• Javelaud D, Besançon F. 2002. Inactivation of p21WAF1 sensitizes cells to apoptosis via an increase of both p14ARF and p53 levels and an alteration of the Bax/Bcl-2 ratio. J. Biol. Chem. 277:37949–37954.
   PubMed Web of Science ®Google Scholar
• Staversky RJ, Vitiello PF, Gehen SC, Helt CE, Rahman A, Keng PC, O'Reilly MA. 2006. p21Cip1/Waf1/Sdi1 protects against hyperoxia by maintaining expression of Bcl-XL. Free Radic. Biol. Med. 41:601–609.
   PubMed Web of Science ®Google Scholar
• Vitiello PF, Staversky RJ, Gehen SC, Johnston CJ, Finkelstein JN, Wright TW, O'Reilly MA. 2006. p21Cip1 protection against hyperoxia requires Bcl-XL and is uncoupled from its ability to suppress growth. Am. J. Pathol. 168:1838–1847.
   PubMed Web of Science ®Google Scholar
• Sullivan KD, Gallant-Behm CL, Henry RE, Fraikin JL, Espinosa JM. 2012. The p53 circuit board. Biochim. Biophys. Acta 1825:229–244.
   PubMedGoogle Scholar
• Shin SY, Kim CG, Lim Y, Lee YH. 2011. The ETS family transcription factor ELK-1 regulates induction of the cell cycle-regulatory gene p21Waf1/Cip1 and the BAX gene in sodium arsenite-exposed human keratinocyte HaCaT cells. J. Biol. Chem. 286:26860–26872.
   PubMedGoogle Scholar
• Lazar DF, Wiese RJ, Brady MJ, Mastick CC, Waters SB, Yamauchi K, Pessin JE, Cuatrecasas P, Saltiel AR. 1995. Mitogen-activated protein kinase kinase inhibition does not block the stimulation of glucose utilization by insulin. J. Biol. Chem. 270:20801–20807.
   PubMedGoogle Scholar
• Cheung M, Sharma A, Madhunapantula SV, Robertson GP. 2008. Akt3 and mutant V600E B-Raf cooperate to promote early melanoma development. Cancer Res. 68:3429–3439.
   PubMed Web of Science ®Google Scholar
• O'Shaughnessy EC, Palani S, Collins JJ, Sarkar CA. 2011. Tunable signal processing in synthetic MAP kinase cascades. Cell 144:119–131.
   PubMedGoogle Scholar
• Kampinga HH, Craig EA. 2010. The HSP70 chaperone machinery: J proteins as drivers of functional specificity. Nat. Rev. Mol. Cell Biol. 11:579–592.
   PubMed Web of Science ®Google Scholar
• Hussussian CJ, Struewing JP, Goldstein AM, Higgins PA, Ally DS, Sheahan MD, Clark WHJr, Tucker MA, Dracopoli NC. 1994. Germline p16 mutations in familial melanoma. Nat. Genet. 8:15–21.
   PubMed Web of Science ®Google Scholar
• Ji Z, Njauw CN, Taylor M, Neel V, Flaherty KT, Tsao H. 2012. p53 rescue through HDM2 antagonism suppresses melanoma growth and potentiates MEK inhibition. J. Invest. Dermatol. 132:356–364.
   PubMedGoogle Scholar
• 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 JRIII, Wright PE, Han J. 2007. PRAK is essential for ras-induced senescence and tumor suppression. Cell 128:295–308.
   PubMed Web of Science ®Google Scholar
• Papetti M, Wontakal SN, Stopka T, Skoultchi AI. 2010. GATA-1 directly regulates p21 gene expression during erythroid differentiation. Cell Cycle 9:1972–1980.
   PubMed Web of Science ®Google Scholar
• Chew YC, Adhikary G, Wilson GM, Xu W, Eckert RL. 2012. Sulforaphane induction of p21Cip1 cyclin-dependent kinase inhibitor expression requires p53 and Sp1 transcription factors and is p53-dependent. J. Biol. Chem. 287:16168–16178.
   PubMedGoogle Scholar
• Solit DB, Rosen N. 2011. Resistance to BRAF inhibition in melanomas. N. Engl. J. Med. 364:772–774.
   PubMed Web of Science ®Google Scholar
• Ventura A, Kirsch DG, McLaughlin ME, Tuveson DA, Grimm J, Lintault L, Newman J, Reczek EE, Weissleder R, Jacks T. 2007. Restoration of p53 function leads to tumour regression in vivo. Nature 445:661–665.
   PubMed Web of Science ®Google Scholar
• Xue W, Zender L, Miething C, Dickins RA, Hernando E, Krizhanovsky V, Cordon-Cardo C, Lowe SW. 2007. Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas. Nature 445:656–660.
   PubMed Web of Science ®Google Scholar
• Bonneau B, Prudent J, Popgeorgiev N, Gillet G. 2013. Non-apoptotic roles of Bcl-2 family: the calcium connection. Biochim. Biophys. Acta 1833:1755–1765.
   PubMed Web of Science ®Google Scholar
• Merrick BA, Walker VR, He C, Patterson RM, Selkirk JK. 1997. Induction of novel Grp75 isoforms by 2-deoxyglucose in human and murine fibroblasts. Cancer Lett. 119:185–190.
   PubMedGoogle Scholar
• Ward PS, Thompson CB. 2012. Metabolic reprogramming: a cancer hallmark even Warburg did not anticipate. Cancer Cell 21:297–308.
   PubMed Web of Science ®Google Scholar
• Gabai VL, Sherman MY, Yaglom JA. 2010. HSP72 depletion suppresses γH2AX activation by genotoxic stresses via p53/p21 signaling. Oncogene 29:1952–1962.
   PubMedGoogle Scholar
• Hupp TR, Meek DW, Midgley CA, Lane DP. 1992. Regulation of the specific DNA binding function of p53. Cell 71:875–886.
   PubMed Web of Science ®Google Scholar
• O'Callaghan-Sunol C, Gabai VL, Sherman MY. 2007. Hsp27 modulates p53 signaling and suppresses cellular senescence. Cancer Res. 67:11779–11788.
   PubMed Web of Science ®Google Scholar
• Walerych D, Kudla G, Gutkowska M, Wawrzynow B, Muller L, King FW, Helwak A, Boros J, Zylicz A, Zylicz M. 2004. Hsp90 chaperones wild-type p53 tumor suppressor protein. J. Biol. Chem. 279:48836–48845.
   PubMed Web of Science ®Google Scholar
• Walerych D, Olszewski MB, Gutkowska M, Helwak A, Zylicz M, Zylicz A. 2009. Hsp70 molecular chaperones are required to support p53 tumor suppressor activity under stress conditions. Oncogene 28:4284–4294.
   PubMed Web of Science ®Google Scholar
• Bukau B, Horwich AL. 1998. The Hsp70 and Hsp60 chaperone machines. Cell 92:351–366.
   PubMed Web of Science ®Google Scholar
• Khalil AA, Kabapy NF, Deraz SF, Smith C. 2011. Heat shock proteins in oncology: diagnostic biomarkers or therapeutic targets? Biochim. Biophys. Acta 1816:89–104.
   PubMed Web of Science ®Google Scholar