The leukemic oncoprotein NPM1-RARA inhibits TP53 activity. Issue 8 (2nd August 2016)

• Record Type: Journal Article
• Authors: Swaney, Erin M.; Chattopadhyay, Anuja; Abecassis, Irina; Rush, Elizabeth A.; Redner, Robert L.
• Is Part Of: Leukemia & lymphoma. Volume 57:Issue 8(2016:Aug.)
• Page Start: 1933
• Page End: 1937
• Publication Date: 2016-08-02
• Subjects: Acute promyelocytic leukemia -- apoptosis -- NPM1-RARA -- nucleophosmin -- TP53; Leukemia -- Periodicals; Lymphomas -- Periodicals; 616.99419
• DOI: 10.3109/10428194.2015.1124992
• Languages: English
• ISSNs: 1042-8194

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.