title: TRP53 activates a global autophagy program to promote tumor suppression.
abstract: The mechanisms by which the TP53/TRP53 transcription factor acts as a tumor suppressor remain incompletely understood. To gain new insights into TP53/TRP53 biology, we used ChIP-seq and RNA-seq technologies to define global TRP53 transcriptional networks in primary cells subjected to DNA damage. Intriguingly, we identified a TRP53-regulated autophagy program, which can be coordinately regulated by the TRP53 family members TRP63 and TRP73 in certain settings. While autophagy is not involved in TRP53-dependent cell cycle arrest, it contributes to both TRP53-driven apoptosis in response to DNA damage and TRP53-mediated transformation suppression. Collectively, our genome-wide analyses reveal a profound role for TRP53 in regulating autophagy, through an extensive transcriptional network, and have demonstrated an important role for this program in promoting TRP53-mediated apoptosis and tumor suppression.
authors.affiliation: Division of Radiation and Cancer Biology; Department of Radiation Oncology; Stanford University School of Medicine; Stanford, CA USA.
authors.forename: Daniela
authors.initials: D
authors.lastname: Kenzelmann Broz
authors.forename: Laura D
authors.initials: LD
authors.lastname: Attardi
mesh_terms: D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D002453:Cell Cycle; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D051379:Mice; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D009687:Nuclear Proteins / Q000378:metabolism; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C000606368:Trp73 protein, mouse; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins
keywords: ChIP-seq; RNA-seq; apoptosis; autophagy; p53; tumor suppression