title: The leukemic oncoprotein NPM1-RARA inhibits TP53 activity.
abstract: The variant acute promyelocytic leukemia (APL) translocation t(5;17)(q35;q21) fuses the N-terminus of nucleophosmin (NPM1) to the retinoic acid receptor alpha (RARA). We found that ectopic NPM1-RARA expression decreased TP53 protein levels in target cells. NPM1-RARA impaired TP53-dependent transcription. Cells expressing NPM1-RARA were more resistant to apoptotic stimuli. This work identifies the TP53 tumor suppressor as a novel target through which NPM1-RARA impacts leukemogenesis, and confirms the importance of impairment of TP53 in establishment of the APL phenotype.
authors.affiliation: a Department of Medicine , University of Pittsburgh, and University of Pittsburgh Cancer Institute, University of Pittsburgh , Pittsburgh , PA , USA.
authors.forename: Erin M
authors.initials: EM
authors.lastname: Swaney
authors.affiliation: a Department of Medicine , University of Pittsburgh, and University of Pittsburgh Cancer Institute, University of Pittsburgh , Pittsburgh , PA , USA.
authors.forename: Anuja
authors.initials: A
authors.lastname: Chattopadhyay
authors.affiliation: a Department of Medicine , University of Pittsburgh, and University of Pittsburgh Cancer Institute, University of Pittsburgh , Pittsburgh , PA , USA.
authors.forename: Irina
authors.initials: I
authors.lastname: Abecassis
authors.affiliation: a Department of Medicine , University of Pittsburgh, and University of Pittsburgh Cancer Institute, University of Pittsburgh , Pittsburgh , PA , USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Rush
authors.affiliation: a Department of Medicine , University of Pittsburgh, and University of Pittsburgh Cancer Institute, University of Pittsburgh , Pittsburgh , PA , USA.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Redner
mesh_terms: D000818:Animals; D017209:Apoptosis; D019556:COS Cells; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism; D002522:Chlorocebus aethiops; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics / Q000473:pathology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D000090243:Nucleophosmin; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism*; D000072482:Retinoic Acid Receptor alpha / Q000235:genetics / Q000378:metabolism*; D014178:Translocation, Genetic; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D020298:U937 Cells
chemical_list: C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; C000607071:RARA protein, human; D000072482:Retinoic Acid Receptor alpha; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D000090243:Nucleophosmin
keywords: Acute promyelocytic leukemia; NPM1-RARA; TP53; apoptosis; nucleophosmin