Back to Search
Start Over
HEXIM1 forms a transcriptionally abortive complex with glucocorticoid receptor without involving 7SK RNA and positive transcription elongation factor b.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2005 Jun 14; Vol. 102 (24), pp. 8555-60. Date of Electronic Publication: 2005 Jun 07. - Publication Year :
- 2005
-
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.
- Subjects :
- Animals
COS Cells
Chlorocebus aethiops
Fluorescent Antibody Technique, Indirect
Glutathione Transferase
HeLa Cells
Humans
Immunoprecipitation
Luciferases
Mass Spectrometry
Nuclear Receptor Coactivator 2
Oligonucleotide Array Sequence Analysis
Protein Binding
Protein Structure, Tertiary
RNA, Small Interfering genetics
Reverse Transcriptase Polymerase Chain Reaction
Transcription Factors metabolism
Transcriptional Activation
Transfection
Gene Expression Regulation
Multiprotein Complexes metabolism
RNA-Binding Proteins metabolism
Receptors, Glucocorticoid metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0027-8424
- Volume :
- 102
- Issue :
- 24
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 15941832
- Full Text :
- https://doi.org/10.1073/pnas.0409863102