ArticleProceedings of the National Academy of Sciences of the United States of America2005
HEXIM1 forms a transcriptionally abortive complex with glucocorticoid receptor without involving 7SK RNA and positive transcription elongation factor b.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 40 citations in OpenAlex.
- cGAS/STING-Independent Induction of Type I Interferon by Inhibitors of the Histone Methylase KDM5B.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Genome-wide CRISPR/Cas9 screen identifies regulators of BCMA expression on multiple myeloma cells.Blood cancer journal · 2024Article
- OverexpressionViruses · 2022Article
- Downregulation of Dihydrotestosterone and Estradiol Levels by HEXIM1.Endocrinology · 2022Article
- HEXIM1 Peptide Exhibits Antimicrobial Activity Against Antibiotic Resistant Bacteria Through Guidance of Cell Penetrating Peptide.Frontiers in microbiology · 2019Article
- Hexim1, an RNA-controlled protein hub.Transcription · 2018Review
- HMBA is a putative HSP70 activator stimulating HEXIM1 expression that is down-regulated by estrogen.The Journal of steroid biochemistry and molecular biology · 2017Article
- Induction of HEXIM1 activities by HMBA derivative 4a1: Functional consequences and mechanism.Cancer letters · 2016Article
- Phosphorylation of HEXIM1 at Tyr271 and Tyr274 Promotes Release of P-TEFb from the 7SK snRNP Complex and Enhances Proviral HIV Gene Expression.Proteomics · 2015Article
- A kinase-independent activity of Cdk9 modulates glucocorticoid receptor-mediated gene induction.Biochemistry · 2014Article
- Lead optimization of HMBA to develop potent HEXIM1 inducers.Bioorganic & medicinal chemistry letters · 2014Article
- RNA polymerase II transcription elongation control.Chemical reviews · 2013Review
- HEXIM1, a New Player in the p53 Pathway.Cancers · 2013Article
- Article
- Identification of HEXIM1 as a positive regulator of p53.The Journal of biological chemistry · 2012Article
- Article
- HEXIM1 modulates vascular endothelial growth factor expression and function in breast epithelial cells and mammary gland.Oncogene · 2010Article
- P-TEFb- the final frontier.Cell division · 2009Article
- Molecular cloning and characterization of the Dicer-like 2 gene from Brassica rapa.Molecular biology reports · 2009Article
- Cyclin T2 is essential for mouse embryogenesis.Molecular and cellular biology · 2009Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The HEXIM1 protein has been shown to form a protein-RNA complex composed of 7SK small nuclear RNA and positive transcription elongation factor b (P-TEFb), which is composed of cyclin-dependent kinase 9 (CDK9) and cyclin T1, and to inhibit the kinase activity of CDK9, thereby suppressing RNA polymerase II-dependent transcriptional elongation. Here, we biochemically demonstrate that HEXIM1 forms a distinct complex with glucocorticoid receptor (GR) without RNA, CDK9, or cyclin T1. HEXIM1, through its arginine-rich nuclear localization signal, directly associates with the ligand-binding domain of GR. Introduction of HEXIM1 short interfering RNA and adenovirus-mediated exogenous expression of HEXIM1 positively and negatively modulated glucocorticoid-responsive gene activation, respectively. In the nucleus, HEXIM1 was shown to localize in a distinct compartment from that of the p160 coactivator transcriptional intermediary factor 2. Overexpression of HEXIM1 decreased ligand-dependent association between GR and transcriptional intermediary factor 2. Antisense-mediated disruption of 7SK blunted the negative effect of HEXIM1 on arylhydrocarbon receptor-dependent transcription but not on GR-mediated one, indicating that a class of transcription factors are direct targets of HEXIM1. These results indicate that HEXIM1 has dual roles in transcriptional regulation: inhibition of transcriptional elongation dependent on 7SK RNA and positive transcription elongation factor b and interference with the sequence-specific transcription factor GR via a direct protein-protein interaction. Moreover, the fact that the central nuclear localization signal of HEXIM1 is essential for both of these actions may argue the crosstalk of these functions.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.