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Title: Hexim1, a new player in the p53 pathway
Authors: Lew, Q.J
Chu, K.L
Chia, Y.L
Cheong, N
Chao, S.-H 
Keywords: hexamethylene bisacetamide inducible protein 1
positive transcription elongation factor b
protein MDM2
protein p53
regulator protein
RNA polymerase II
unclassified drug
acute granulocytic leukemia
binding affinity
protein expression
protein function
protein localization
protein protein interaction
signal transduction
transcription regulation
Issue Date: 2013
Citation: Lew, Q.J, Chu, K.L, Chia, Y.L, Cheong, N, Chao, S.-H (2013). Hexim1, a new player in the p53 pathway. Cancers 5 (3) : 838-856. ScholarBank@NUS Repository.
Rights: Attribution 4.0 International
Abstract: Hexamethylene bisacetamide-inducible protein 1 (HEXIM1) is best known as the inhibitor of positive transcription elongation factor b (P-TEFb), which controls transcription elongation of RNA polymerase II and Tat transactivation of human immunodeficiency virus. Besides P-TEFb, several proteins have been identified as HEXIM1 binding proteins. It is noteworthy that more than half of the HEXIM1 binding partners are involved in cancers. P53 and two key regulators of the p53 pathway, nucleophosmin (NPM) and human double minute-2 protein (HDM2), are among the factors identified. This review will focus on the functional importance of the interactions between HEXIM1 and p53/NPM/HDM2. NPM and the cytoplasmic mutant of NPM, NPMc+, were found to regulate P-TEFb activity and RNA polymerase II transcription through the interaction with HEXIM1. Importantly, more than one-third of acute myeloid leukemia (AML) patients carry NPMc+, suggesting the involvement of HEXIM1 in tumorigenesis of AML. HDM2 was found to ubiquitinate HEXIM1. The HDM2-mediated ubiquitination of HEXIM1 did not lead to protein degradation of HEXIM1 but enhanced its inhibitory activity on P-TEFb. Recently, HEXIM1 was identified as a novel positive regulator of p53. HEXIM1 prevented p53 ubiquitination by competing with HDM2 in binding to p53. Taken together, the new evidence suggests a role of HEXIM1 in regulating the p53 pathway and tumorigenesis. © 2013 by the authors; licensee MDPI, Basel, Switzerland.
Source Title: Cancers
ISSN: 20726694
Rights: Attribution 4.0 International
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