The leukemic oncoprotein NPM1-RARA inhibits TP53 activity.

Swaney, Erin M; Chattopadhyay, Anuja; Abecassis, Irina; Rush, Elizabeth A; Redner, Robert L

Swaney, Erin M; Chattopadhyay, Anuja; Abecassis, Irina; Rush, Elizabeth A; Redner, Robert L.

Afiliação

Swaney EM; a Department of Medicine , University of Pittsburgh, and University of Pittsburgh Cancer Institute, University of Pittsburgh , Pittsburgh , PA , USA.
Chattopadhyay A; a Department of Medicine , University of Pittsburgh, and University of Pittsburgh Cancer Institute, University of Pittsburgh , Pittsburgh , PA , USA.
Abecassis I; a Department of Medicine , University of Pittsburgh, and University of Pittsburgh Cancer Institute, University of Pittsburgh , Pittsburgh , PA , USA.
Rush EA; a Department of Medicine , University of Pittsburgh, and University of Pittsburgh Cancer Institute, University of Pittsburgh , Pittsburgh , PA , USA.
Redner RL; a Department of Medicine , University of Pittsburgh, and University of Pittsburgh Cancer Institute, University of Pittsburgh , Pittsburgh , PA , USA.

Leuk Lymphoma ; 57(8): 1933-7, 2016 08.

Article em En | MEDLINE | ID: mdl-26754533

ABSTRACT

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.

Assuntos

Leucemia Promielocítica Aguda/patologia; Proteínas Nucleares/metabolismo; Proteínas de Fusão Oncogênica/metabolismo; Receptor alfa de Ácido Retinoico/metabolismo; Proteína Supressora de Tumor p53/metabolismo; Animais; Apoptose; Células COS; Carcinogênese/genética; Carcinogênese/metabolismo; Chlorocebus aethiops; Cromossomos Humanos Par 17/genética; Cromossomos Humanos Par 5/genética; Humanos; Leucemia Promielocítica Aguda/genética; Proteínas Nucleares/genética; Nucleofosmina; Proteínas de Fusão Oncogênica/genética; Receptor alfa de Ácido Retinoico/genética; Translocação Genética; Células U937

Palavras-chave

Acute promyelocytic leukemia; NPM1-RARA; TP53; apoptosis; nucleophosmin

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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas Nucleares / Leucemia Promielocítica Aguda / Proteínas de Fusão Oncogênica / Proteína Supressora de Tumor p53 / Receptor alfa de Ácido Retinoico Limite: Animals / Humans Idioma: En Revista: Leuk Lymphoma Assunto da revista: HEMATOLOGIA / NEOPLASIAS Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Estados Unidos

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