title: KIAA1524/CIP2A promotes cancer growth by coordinating the activities of MTORC1 and MYC.
abstract: KIAA1524/CIP2A/cancerous inhibitor of protein phosphatase 2A is a cancer-promoting protein that stabilizes the MYC proto-oncogene protein by inhibiting its dephosphorylation. Our recent report demonstrates that KIAA1524/CIP2A supports cancer cell growth also at the level of the mechanistic target of rapamycin complex 1 (MTORC1), a key signaling module that drives cell growth by stimulating protein synthesis and inhibiting autophagy. KIAA1524/CIP2A suppresses MTORC1-associated protein phosphatase 2A (PP2A) activity in an allosteric manner thereby stabilizing the phosphorylation of MTORC1 substrates and keeping the cell in an anabolic mode. In the absence of growth stimulating signals or nutrients, reduced MTORC1 activity triggers SQSTM1/p62-dependent autophagic degradation of KIAA1524/CIP2A enhancing the PP2A-mediated dephosphorylation of MTORC1 substrates and MYC. Thus, KIAA1524/CIP2A emerges as an oncoprotein that can coordinate the growth-promoting activities of MTORC1 and MYC in response to environmental and intrinsic cues.
authors.affiliation: Cell Death and Metabolism; Danish Cancer Society Research Center (DCRC); Copenhagen, Denmark.
authors.forename: Pietri
authors.initials: P
authors.lastname: Puustinen
authors.affiliation: Cell Death and Metabolism; Danish Cancer Society Research Center (DCRC); Copenhagen, Denmark.
authors.forename: Marja
authors.initials: M
authors.lastname: Jäättelä
mesh_terms: D001343:Autophagy; D049109:Cell Proliferation; D025461:Feedback, Physiological; D006801:Humans; D000076222:Mechanistic Target of Rapamycin Complex 1; D008565:Membrane Proteins / Q000378:metabolism; D008954:Models, Biological; D046912:Multiprotein Complexes / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D054648:Protein Phosphatase 2 / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: C000715470:MAS1 protein, human; D008565:Membrane Proteins; D046912:Multiprotein Complexes; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D054648:Protein Phosphatase 2
keywords: CIP2A; Myc; autophagy; cancer; phosphatase