The leukemic oncoprotein NPM1-RARA inhibits TP53 activity
- Resource Type
- Authors
- Irina Abecassis; Erin M. Swaney; Elizabeth A. Rush; Anuja Chattopadhyay; Robert L. Redner
- Source
- Leukemia & Lymphoma. 57:1933-1937
- Subject
- 0301 basic medicine
Acute promyelocytic leukemia
Cancer Research
NPM1
Oncogene Proteins, Fusion
endocrine system diseases
Carcinogenesis
Apoptosis
Chromosomal translocation
medicine.disease_cause
Translocation, Genetic
Article
03 medical and health sciences
Promyelocytic leukemia protein
Leukemia, Promyelocytic, Acute
Chlorocebus aethiops
medicine
Animals
Humans
Nuclear protein
neoplasms
Nucleophosmin
biology
Retinoic Acid Receptor alpha
Nuclear Proteins
U937 Cells
Hematology
medicine.disease
030104 developmental biology
Oncology
Retinoic acid receptor alpha
COS Cells
biology.protein
Cancer research
Chromosomes, Human, Pair 5
Tumor Suppressor Protein p53
Chromosomes, Human, Pair 17
- Language
- ISSN
- 1029-2403
1042-8194
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.