ArticleThe Journal of biological chemistry2012
Identification of HEXIM1 as a positive regulator of p53.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 38 citations in OpenAlex.
- 7SK small nuclear RNA (Rn7SK) induces apoptosis through intrinsic and extrinsic pathways in human embryonic kidney cell line.Molecular biology reports · 2024Article
- HMBA ameliorates obesity by MYH9- and ACTG1-dependent regulation of hypothalamic neuropeptides.EMBO molecular medicine · 2023Article
- Nuclear stabilization of p53 requires a functional nucleolar surveillance pathway.Cell reports · 2022Article
- Combination of Talazoparib and Palbociclib as a Potent Treatment Strategy in Bladder Cancer.Journal of personalized medicine · 2021Article
- Construction and validation of an RNA-binding protein-associated prognostic model for colorectal cancer.PeerJ · 2021Article
- Non-epigenetic induction of HEXIM1 by DNMT1 inhibitors and functional relevance.Scientific reports · 2020Article
- Article
- Role of the ERO1-PDI interaction in oxidative protein folding and disease.Pharmacology & therapeutics · 2020Review
- Inhibition of the histone demethylase, KDM5B, directly induces re-expression of tumor suppressor protein HEXIM1 in cancer cells.Breast cancer research : BCR · 2019Article
- HEXIM1 Diffusion in the Nucleus Is Regulated by Its Interactions with Both 7SK and P-TEFb.Biophysical journal · 2019Article
- BET Inhibition Induces HEXIM1- and RAD51-Dependent Conflicts between Transcription and Replication.Cell reports · 2018Article
- Transcriptomic Analysis Implicates the p53 Signaling Pathway in the Establishment of HIV-1 Latency in Central Memory CD4 T Cells in an In Vitro Model.PLoS pathogens · 2016Article
- Induction of HEXIM1 activities by HMBA derivative 4a1: Functional consequences and mechanism.Cancer letters · 2016Article
- Article
- A comprehensive and high-resolution genome-wide response of p53 to stress.Cell reports · 2014Article
- Brd4 and HEXIM1: multiple roles in P-TEFb regulation and cancer.BioMed research international · 2014Review
- Chronic inflammation and cancer: potential chemoprevention through nuclear factor kappa B and p53 mutual antagonism.Journal of inflammation (London, England) · 2014Review
- RNA polymerase II transcription elongation control.Chemical reviews · 2013Review
- Aptamer identification of brain tumor-initiating cells.Cancer research · 2013Article
- HEXIM1, a New Player in the p53 Pathway.Cancers · 2013Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hexamethylene bisacetamide-inducible protein 1 (HEXIM1) is best known as the inhibitor of positive transcription elongation factor b (P-TEFb), which regulates the transcription elongation of RNA polymerase II and controls 60-70% of mRNA synthesis. Our previous studies show that HEXIM1 interacts with two key p53 regulators, nucleophosmin and human double minute-2 protein (HDM2), implying a possible connection between HEXIM1 and the p53 signaling pathway. Here we report the interaction between p53 and HEXIM1 in breast cancer, acute myeloid leukemia, and colorectal carcinoma cells. The C-terminal regions of p53 and HEXIM1 are required for the protein-protein interaction. Overexpression of HEXIM1 prevents the ubiquitination of p53 by HDM2 and enhances the protein stability of p53, resulting in up-regulation of p53 target genes, such as Puma and p21. Induction of p53 can be achieved by several means, such as UV radiation and treatment with anti-cancer agents (including doxorubicin, etoposide, roscovitine, flavopiridol, and nutlin-3). Under all the conditions examined, elevated protein levels of p53 are found to associate with the increased p53-HEXIM1 interaction. In addition, knockdown of HEXIM1 significantly inhibits the induction of p53 and releases the cell cycle arrest caused by p53. Finally, the transcription of the p53 target genes is regulated by HEXIM1 in a p53-dependent fashion. Our results not only identify HEXIM1 as a positive regulator of p53, but also propose a novel molecular mechanism of p53 activation caused by the anti-cancer drugs and compounds.
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