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Maf1 is a novel target of PTEN and PI3K signaling that negatively regulates oncogenesis and lipid metabolism.
Palian, Beth M; Rohira, Aarti D; Johnson, Sandra A S; He, Lina; Zheng, Ni; Dubeau, Louis; Stiles, Bangyan L; Johnson, Deborah L.
Afiliación
  • Palian BM; Department of Biochemistry and Molecular Biology, Keck School of Medicine, University of Southern California, and the Norris Comprehensive Cancer Center, Los Angeles, California, United States of America.
  • Rohira AD; Department of Biochemistry and Molecular Biology, Keck School of Medicine, University of Southern California, and the Norris Comprehensive Cancer Center, Los Angeles, California, United States of America.
  • Johnson SA; Department of Biochemistry and Molecular Biology, Keck School of Medicine, University of Southern California, and the Norris Comprehensive Cancer Center, Los Angeles, California, United States of America.
  • He L; Department of Pharmaceutical Sciences, School of Pharmacy, Keck School of Medicine, University of Southern California, and the Norris Comprehensive Cancer Center, Los Angeles, California, United States of America.
  • Zheng N; Department of Pharmaceutical Sciences, School of Pharmacy, Keck School of Medicine, University of Southern California, and the Norris Comprehensive Cancer Center, Los Angeles, California, United States of America.
  • Dubeau L; Department of Pathology, Keck School of Medicine, University of Southern California, and the Norris Comprehensive Cancer Center, Los Angeles, California, United States of America.
  • Stiles BL; Department of Pharmaceutical Sciences, School of Pharmacy, Keck School of Medicine, University of Southern California, and the Norris Comprehensive Cancer Center, Los Angeles, California, United States of America.
  • Johnson DL; Department of Biochemistry and Molecular Biology, Keck School of Medicine, University of Southern California, and the Norris Comprehensive Cancer Center, Los Angeles, California, United States of America.
PLoS Genet ; 10(12): e1004789, 2014 Dec.
Article en En | MEDLINE | ID: mdl-25502566
Maf1 was initially identified as a transcriptional repressor of RNA pol III-transcribed genes, yet little is known about its other potential target genes or its biological function. Here, we show that Maf1 is a key downstream target of PTEN that drives both its tumor suppressor and metabolic functions. Maf1 expression is diminished with loss of PTEN in both mouse models and human cancers. Consistent with its role as a tumor suppressor, Maf1 reduces anchorage-independent growth and tumor formation in mice. PTEN-mediated changes in Maf1 expression are mediated by PTEN acting on PI3K/AKT/FoxO1 signaling, revealing a new pathway that regulates RNA pol III-dependent genes. This regulatory event is biologically relevant as diet-induced PI3K activation reduces Maf1 expression in mouse liver. We further identify lipogenic enzymes as a new class of Maf1-regulated genes whereby Maf1 occupancy at the FASN promoter opposes SREBP1c-mediated transcription activation. Consistent with these findings, Maf1 inhibits intracellular lipid accumulation and increasing Maf1 expression in mouse liver abrogates diet-mediated induction of lipogenic enzymes and triglycerides. Together, these results establish a new biological role for Maf1 as a downstream effector of PTEN/PI3K signaling and reveal that Maf1 is a key element by which this pathway co-regulates lipid metabolism and oncogenesis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Represoras / Fosfatidilinositol 3-Quinasas / Fosfohidrolasa PTEN / Metabolismo de los Lípidos / Carcinogénesis Tipo de estudio: Prognostic_studies Límite: Animals / Humans / Male Idioma: En Revista: PLoS Genet Asunto de la revista: GENETICA Año: 2014 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Represoras / Fosfatidilinositol 3-Quinasas / Fosfohidrolasa PTEN / Metabolismo de los Lípidos / Carcinogénesis Tipo de estudio: Prognostic_studies Límite: Animals / Humans / Male Idioma: En Revista: PLoS Genet Asunto de la revista: GENETICA Año: 2014 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos