Affinage

HEXIM1

Protein HEXIM1 · UniProt O94992

Length
359 aa
Mass
40.6 kDa
Annotated
2026-04-28
100 papers in source corpus 37 papers cited in narrative 35 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HEXIM1 is a key negative regulator of transcription elongation that functions as the RNA-dependent inhibitor of the positive transcription elongation factor b (P-TEFb, CDK9/cyclin T). HEXIM1 binds 7SK snRNA through its arginine-rich motif at the 5' hairpin GAUC repeat, triggering a conformational change that enables its C-terminal coiled-coil homodimer domain to engage cyclin T1 and its conserved PYNT motif (F208) to contact the CDK9 activation segment, blocking substrate access to the catalytic cleft and inactivating P-TEFb kinase activity (PMID:14580347, PMID:15201869, PMID:27791144, PMID:17724342). This inhibition is dynamically regulated by phosphorylation (PKC at S158 disrupts 7SK binding; Akt-mediated phosphorylation releases P-TEFb), by HIV-1 Tat competing for cyclin T1, and by PPM1G blocking snRNP reassembly through a 7SK conformational change, while HEXIM2 provides functional compensation to maintain cellular P-TEFb equilibrium (PMID:22821562, PMID:17937499, PMID:17341462, PMID:20808803, PMID:15713661). Beyond P-TEFb regulation, HEXIM1 stabilizes p53 by preventing HDM2-mediated ubiquitination, forms a NEAT1 lncRNA-dependent HDP-RNP complex that activates innate immune signaling through the cGAS-STING-IRF3 pathway, directly modulates glucocorticoid and estrogen receptor-dependent transcription, and is essential for cardiovascular development, as mouse knockout causes prenatal lethality with cardiac hypertrophy and defective coronary vascularization (PMID:22948151, PMID:28712728, PMID:15941832, PMID:18757415, PMID:15172687, PMID:18079413).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 2003 High

    Establishing HEXIM1 as the 7SK-dependent inhibitor of P-TEFb resolved the long-standing question of how the kinase is held inactive in the large nuclear complex and revealed that 7SK RNA is required not just for scaffolding but for enabling HEXIM1–P-TEFb interaction.

    Evidence In vivo/in vitro transcription assays, co-IP, and mass spectrometry in two independent studies

    PMID:12832472 PMID:14580347

    Open questions at the time
    • Mechanism by which 7SK enables HEXIM1 binding to P-TEFb was unknown
    • Stoichiometry of the inhibitory complex was unresolved
    • Signals governing reversible assembly were undefined
  2. 2004 High

    Domain dissection established a sequential assembly model: the HEXIM1 arginine-rich motif first binds 7SK RNA, and this binding is a prerequisite that then allows the C-terminal domain (aa 181–359) to contact P-TEFb, with a conserved motif at aa 202–205 required specifically for kinase inhibition.

    Evidence In vitro reconstitution with purified proteins, yeast three-hybrid, gel-shift, GST pull-down, mutagenesis across multiple studies

    PMID:15169877 PMID:15201869

    Open questions at the time
    • Structural basis for 7SK-induced conformational change in HEXIM1 was unknown
    • Exact contact surface on CDK9/cyclin T1 was not mapped
  3. 2004 High

    Mouse HEXIM1 knockout revealed an essential developmental role: loss of HEXIM1 causes prenatal lethality with cardiac hypertrophy and downregulation of HAND1, establishing HEXIM1 as indispensable for normal cardiovascular development.

    Evidence Gene knockout in mice with cardiac phenotype, electron microscopy, Northern blot

    PMID:15172687

    Open questions at the time
    • Whether cardiac phenotype is solely due to deregulated P-TEFb was untested
    • HEXIM2 compensation in heart was not assessed
  4. 2005 High

    Determination that the large P-TEFb complex contains a HEXIM1 homodimer (via coiled-coil domain) bridging two P-TEFb molecules, and that HEXIM2 can functionally compensate for HEXIM1 loss, revealed the precise stoichiometry and redundancy safeguarding P-TEFb regulation.

    Evidence Glycerol gradient sedimentation, stoichiometry analysis, mutagenesis, HEXIM1 knockdown with HEXIM2 compensation assays

    PMID:15713661 PMID:15713662 PMID:15965233

    Open questions at the time
    • Signals determining HEXIM1 vs. HEXIM2 usage were unclear
    • Whether heterodimers have distinct regulatory properties was untested
  5. 2005 High

    Biophysical characterization of the cyclin T-binding domain and the discovery that HIV-1 Tat competes with HEXIM1 for cyclin T1 binding defined the molecular basis for P-TEFb hijacking during HIV transcription activation.

    Evidence GST pull-down, ITC, fluorescence spectroscopy, analytical gel filtration, HeLa functional assays

    PMID:15855166 PMID:15941832

    Open questions at the time
    • Structural detail of the Tat–cyclin T1–HEXIM1 competition interface was lacking
    • Whether GR interaction competes with P-TEFb binding was not fully resolved
  6. 2005 High

    Identification of a HEXIM1–glucocorticoid receptor complex independent of 7SK/P-TEFb established that HEXIM1 has functions beyond P-TEFb inhibition, acting as a direct nuclear receptor coregulator.

    Evidence Co-IP, domain mapping, siRNA knockdown, antisense-mediated 7SK disruption

    PMID:15941832

    Open questions at the time
    • Physiological significance of HEXIM1–GR interaction in glucocorticoid target tissues was not established
    • Mechanism by which HEXIM1 displaces TIF2 from GR was unknown
  7. 2006 High

    Mapping distinct 7SK RNA elements for HEXIM1 and P-TEFb binding (5' hairpin for HEXIM1, 3' hairpin for P-TEFb) established that HEXIM1 binding to the 5' element is a prerequisite for P-TEFb loading onto the 3' element, explaining hierarchical snRNP assembly.

    Evidence Systematic 7SK mutagenesis, in vivo RNA-protein binding assays, minimal RNA reconstitution

    PMID:16382153

    Open questions at the time
    • Contributions of LARP7 and MePCE to this hierarchical assembly were unknown
    • Whether the two 7SK elements communicate allosterically was untested
  8. 2007 High

    The NMR structure of the HEXIM1 cyclin T-binding domain revealed a parallel coiled-coil homodimer with an electrostatic binding interface for cyclin T1, and photo-cross-linking showed that HEXIM1 F208 directly contacts the CDK9 activation segment, establishing a dual-contact inhibition mechanism blocking both cyclin T and CDK9 substrate access.

    Evidence NMR solution structure, NMR titration, fluorescence, mutagenesis; site-specific photo-cross-linking in live cells and reconstituted complexes with MS identification

    PMID:17724342 PMID:27791144

    Open questions at the time
    • Full atomic-resolution structure of the entire 7SK–HEXIM1–P-TEFb complex was lacking
    • Whether HEXIM1 also contacts CDK9 outside the activation segment was unresolved
  9. 2007 High

    Demonstration that HIV-1 Tat directly displaces HEXIM1 from preformed 7SK snRNP in vitro and in primary lymphocytes, and that Akt-mediated HEXIM1 phosphorylation independently releases P-TEFb, established two distinct molecular routes for P-TEFb activation relevant to HIV latency reversal.

    Evidence In vitro competition with purified proteins, glycerol gradients, PI3K/Akt inhibitors, phosphorylation-resistant HEXIM1 mutants, primary cell analysis

    PMID:17341462 PMID:17576689 PMID:17937499

    Open questions at the time
    • Specific Akt phosphorylation site on HEXIM1 was not mapped in this study
    • Relative contribution of Tat displacement vs. phosphorylation during actual HIV infection was unclear
  10. 2007 High

    Insertional mutagenesis confirmed HEXIM1's cardiac essentiality and identified VEGF as a direct transcriptional target, showing HEXIM1 attenuates C/EBPα-mediated repression of VEGF, linking P-TEFb regulation to coronary vascularization.

    Evidence Mouse insertional mutation, PECAM-1 staining, ChIP at VEGF promoter, qRT-PCR

    PMID:18079413

    Open questions at the time
    • Whether HEXIM1 regulation of VEGF is P-TEFb-dependent or through the C/EBPα mechanism alone was unresolved
  11. 2007 High

    Discovery that hypertrophic stimuli trigger HEXIM1 dissociation from P-TEFb via JAK/STAT signaling in cardiomyocytes connected P-TEFb reactivation to pathological cardiac hypertrophy.

    Evidence Co-IP in primary cardiomyocytes, mechanical stretch, endothelin-1, JAK2 inhibitor AG490

    PMID:17459355

    Open questions at the time
    • Direct JAK2 target (HEXIM1 itself or an intermediary) was not identified
    • Whether this mechanism operates in vivo during heart failure was untested
  12. 2008 High

    Identification of LARP7 as the constitutive 7SK snRNP scaffold, with HEXIM1 and P-TEFb as reversible components, clarified the dynamic architecture of the snRNP and explained how 7SK stability is maintained independently of P-TEFb occupancy.

    Evidence Immunodepletion, glycerol gradient sedimentation, siRNA knockdown, Tat transactivation assays

    PMID:18281698

    Open questions at the time
    • MePCE's role relative to LARP7 in snRNP stability was not fully addressed
    • Whether HEXIM1 can exist as a stable 7SK-bound intermediate without P-TEFb in vivo was debated
  13. 2008 High

    Nucleophosmin (NPM) was identified as a negative regulator that binds HEXIM1 and promotes its proteasomal degradation; the AML-associated cytoplasmic NPMc+ mutant sequesters HEXIM1, providing a disease mechanism linking HEXIM1 inactivation to leukemogenesis.

    Evidence Reciprocal co-IP, GST pull-down, proteasome inhibitor rescue, subcellular fractionation with NPMc+ mutant

    PMID:18371977

    Open questions at the time
    • E3 ubiquitin ligase responsible for NPM-induced HEXIM1 degradation was not identified
    • In vivo relevance in AML patient samples was not shown
  14. 2010 High

    NMR revealed that HEXIM1 ARM binding induces opening of the GAUC motif in 7SK's 5' hairpin, and that P-TEFb release by Tat/Brd4 causes a major 7SK conformational change blocking HEXIM1 re-association, establishing HEXIM1 reincorporation as the rate-limiting step of snRNP reassembly.

    Evidence NMR spectroscopy of 7SK–ARM complex, SHAPE/DMS probing of released 7SK, in vitro release assays from immunopurified snRNP

    PMID:20675720 PMID:20808803

    Open questions at the time
    • Factor(s) responsible for resetting 7SK conformation to allow HEXIM1 rebinding were unknown
    • Whether the conformational switch operates identically for HEXIM2 was untested
  15. 2012 High

    PKC phosphorylation of HEXIM1 at S158 was shown to abolish 7SK binding and P-TEFb inhibition, defining a direct signaling mechanism for P-TEFb activation downstream of TCR engagement.

    Evidence In vitro kinase assay, S158A phospho-resistant mutant, T cell activation assays, glycerol gradients

    PMID:22821562

    Open questions at the time
    • Whether other kinases also target S158 was not excluded
    • Phosphatase(s) reversing S158 phosphorylation were not identified
  16. 2012 High

    HEXIM1 was shown to stabilize p53 by directly binding its C-terminus and preventing HDM2-mediated ubiquitination, establishing a P-TEFb-independent tumor suppressor function.

    Evidence Co-IP, ubiquitination assays, siRNA knockdown, cell cycle analysis in multiple cancer cell lines

    PMID:22948151

    Open questions at the time
    • Whether HEXIM1–p53 interaction occurs in the context of 7SK snRNP or free HEXIM1 was unclear
    • In vivo tumor suppression via p53 stabilization was not directly tested
  17. 2015 High

    PPM1G phosphatase was found to bind both 7SK and HEXIM1 after P-TEFb release, blocking snRNP reassembly to sustain NF-κB transcription elongation under ATM kinase control, revealing a regulated 'lock' on the disassembled state.

    Evidence Direct in vitro binding assays, ChIP kinetics, ATM inhibition experiments

    PMID:26324325

    Open questions at the time
    • PPM1G's phosphatase substrates relevant to this locking mechanism were not identified
    • Whether PPM1G competes with HEXIM1 for the same 7SK binding site was unresolved
  18. 2016 High

    Nucleotide stress was shown to induce HEXIM1 to suppress transcription at tumorigenic loci; HEXIM1 overexpression suppressed melanoma in zebrafish while its loss accelerated tumor onset, providing direct genetic evidence for HEXIM1 as a tumor suppressor.

    Evidence Zebrafish gain/loss-of-function melanoma model, RNA immunoprecipitation, human melanoma cell knockdown

    PMID:27058786

    Open questions at the time
    • Identity and mechanism of anti-tumorigenic RNAs stabilized by HEXIM1 were not fully characterized
    • Whether the tumor-suppressive effect requires P-TEFb inhibition specifically was not dissected
  19. 2017 High

    Discovery of the HDP-RNP complex (HEXIM1–NEAT1–DNA-PK–paraspeckle proteins) and its role in cGAS-STING-IRF3 innate immune signaling revealed a major P-TEFb-independent function: HEXIM1 scaffolds an RNA-dependent complex that senses foreign DNA and activates interferon responses.

    Evidence IP/MS, RNA-seq, siRNA knockdown, cGAS-STING pathway activation assays

    PMID:28712728

    Open questions at the time
    • Whether HEXIM1's RNA-binding specificity for NEAT1 vs. 7SK determines partitioning between P-TEFb and HDP-RNP functions was unclear
    • Structural basis of HDP-RNP assembly was unknown
  20. 2019 High

    KDM5B was identified as a direct transcriptional repressor of HEXIM1 via H3K4 demethylation at its promoter; KDM5B inhibition upregulates HEXIM1 and suppresses breast tumor metastasis, defining an epigenetic input controlling HEXIM1 expression in cancer.

    Evidence Chemical proteomics, SPR, ChIP at HEXIM1 promoter, shRNA knockdown, mouse metastasis model

    PMID:31805991

    Open questions at the time
    • Whether other KDM5 family members also regulate HEXIM1 was not tested
    • Therapeutic window of KDM5B inhibition via HEXIM1 induction was not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major unresolved questions include the full atomic structure of the 7SK–HEXIM1–P-TEFb ternary complex, the molecular basis for partitioning HEXIM1 between 7SK snRNP and HDP-RNP functions, the identity of E3 ligases controlling HEXIM1 turnover, and how P-TEFb-dependent and -independent tumor suppressor activities of HEXIM1 are coordinated in vivo.
  • No high-resolution structure of the full ternary inhibitory complex
  • Mechanism of HEXIM1 allocation between 7SK snRNP and NEAT1-based HDP-RNP is unknown
  • E3 ligase for HEXIM1 ubiquitination/degradation has not been identified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 6 GO:0098772 molecular function regulator activity 5 GO:0140110 transcription regulator activity 3
Localization
GO:0005634 nucleus 3 GO:0005654 nucleoplasm 2 GO:0005829 cytosol 2
Pathway
R-HSA-74160 Gene expression (Transcription) 7 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-1266738 Developmental Biology 2 R-HSA-168256 Immune System 2 R-HSA-5357801 Programmed Cell Death 1
Partners
CCNT1CDK9HEXIM2LARP7NPM1NR3C1PPM1GTP53
Complex memberships
7SK snRNPHDP-RNP

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 HEXIM1 (MAQ1) inhibits P-TEFb (CDK9/cyclin T) kinase activity in a process that specifically requires 7SK snRNA to mediate the HEXIM1:P-TEFb interaction; 7SK binding alone is insufficient to inhibit P-TEFb, and P-TEFb dissociates from HEXIM1 and 7SK during stress response. In vivo and in vitro transcription assays, immunoprecipitation, mass spectrometry identification of complex components Molecular cell High 12832472 14580347
2004 HEXIM1 binds 7SK snRNA directly through a central arginine-rich RNA-binding motif (amino acids 152-155), and the HEXIM1 C-terminal domain (aa 181-359) directly binds P-TEFb; a conserved motif (aa 202-205) is required for P-TEFb binding and inhibition but not for 7SK recognition, establishing a sequential assembly model. In vitro reconstitution of 7SK-dependent HEXIM1-P-TEFb complex with purified proteins, yeast three-hybrid tests, gel-shift assays, GST pull-down, yeast two-hybrid, point mutagenesis The EMBO journal High 15201869
2004 The first 18 amino acids within the NLS of HEXIM1 constitute an arginine-rich motif (resembling HIV-1 Tat TAR-binding domain) that is necessary and sufficient for 7SK binding in vivo and in vitro; this motif is essential for HEXIM1's inhibitory action on P-TEFb and RNA Pol II transcription. In vivo and in vitro 7SK binding assays, HEXIM1 deletion/substitution mutants, immunoprecipitation, in vitro kinase assays Molecular and cellular biology High 15169877
2005 The large inactive P-TEFb complex contains one 7SK molecule, a HEXIM1 dimer (mediated by a C-terminal coiled-coil region), and two P-TEFb molecules; CDK9 phosphorylated at Thr186 is required for P-TEFb recruitment to the 7SK/HEXIM complex; conserved residues Tyr271 and Phe208 in HEXIM1 are required for P-TEFb inhibition but not complex formation. Mutational analysis, glycerol gradient sedimentation, in vitro kinase assays, stoichiometry analysis The Journal of biological chemistry High 15965233
2005 HEXIM1 contains a stable C-terminal cyclin T-binding domain (TBD, residues 255-359) that forms a coiled-coil homodimer and directly binds the cyclin boxes of cyclin T1; HIV-1 Tat competes with HEXIM1 for cyclin T1 binding, displacing HEXIM1 from the P-TEFb complex. GST pull-down, analytical gel filtration, isothermal titration calorimetry, fluorescence spectroscopy, size exclusion chromatography, HeLa cell functional assays The Journal of biological chemistry High 15855166
2005 HEXIM1's basic region contains two monopartite and two bipartite nuclear localization sequences; the arginine-rich motif within the basic region is essential for 7SK snRNA binding, P-TEFb binding, and transcription inhibition; the basic region interacts with adjacent acidic regions in the absence of RNA, and removal of negative charges causes HEXIM1 sequestration into the large complex and nuclear speckle localization. NLS-deletion mutagenesis, immunofluorescence, subnuclear localization studies, in vivo transcription assays The EMBO journal High 16362050
2005 HEXIM1 forms oligomers (most likely dimers) mediated by its C-terminal coiled-coil region and by 7SK snRNA binding to the central basic region; mutations in the N-terminal part of the coiled-coil abrogate P-TEFb binding and inhibition; oligomerization via both the coiled-coil and basic regions is critical for inhibition of transcriptional elongation. Alanine mutagenesis of conserved leucines, RNase A digestion, co-immunoprecipitation, in vivo transcription assays Nucleic acids research High 16377779
2005 HEXIM1 and HEXIM2 can form stable homo- and hetero-oligomers (most likely dimers); HEXIM2 compensates functionally for HEXIM1 loss to maintain constant levels of 7SK/HEXIM-bound P-TEFb, demonstrating a tightly regulated cellular mechanism balancing active and inactive P-TEFb. Immunoprecipitation, glycerol gradient sedimentation, HEXIM1 knockdown/HEXIM2 compensation assays, in vivo transcription assays The Journal of biological chemistry High 15713661 15713662
2006 Two structurally distinct RNA elements in 7SK—the distal segment of the 5' hairpin (G24-C48/G60-C87) and the apical region of the 3' hairpin (G302-C324)—independently recruit HEXIM1 and P-TEFb respectively; HEXIM1 binding to the 5' hairpin is a prerequisite for P-TEFb association with the 3' hairpin. In vivo RNA-protein binding assays, mutagenesis of 7SK elements, HeLa cell transcription assays, minimal regulatory RNA reconstitution Molecular and cellular biology High 16382153
2007 HEXIM1 directly contacts CDK9 at its activation segment (near the catalytic cleft); the conserved PYNT sequence (aa 202-205) of HEXIM1, specifically F208, cross-links to a Cdk9 peptide within the activation segment controlling access to the catalytic cleft, suggesting HEXIM1 inhibits P-TEFb by interfering with substrate binding to CDK9. Photo-cross-linking with photoreactive amino acids in live cells, cell extracts, and in vitro reconstituted complexes; mass spectrometry identification of cross-linked peptides Proceedings of the National Academy of Sciences of the United States of America High 27791144
2007 The solution structure of the HEXIM1 cyclin T-binding domain (TBD) reveals a parallel coiled-coil homodimer with a preceding alpha helix folding back onto the first coiled-coil unit; NMR titration, fluorescence, and immunoprecipitation identify the binding interface covering the first coiled-coil segment, with electrostatic interactions between an acidic patch on HEXIM1 and positive residues of cyclin T1 driving complex formation. NMR solution structure determination, NMR titration, fluorescence spectroscopy, immunoprecipitation, mutagenesis with transcription regulation assays in cells Proceedings of the National Academy of Sciences of the United States of America High 17724342
2007 HIV-1 Tat prevents formation of and releases P-TEFb from the 7SK snRNP by directly displacing HEXIM1 from cyclin T1 through high-affinity Tat-cyclin T1 interaction; in vitro, Tat competes with HEXIM1 for 7SK binding and can release P-TEFb from preformed P-TEFb-HEXIM1-7SK complex; primary blood lymphocytes show reduced 7SK snRNP upon HIV-1 infection. In vitro competition assays with purified proteins, immunoprecipitation in vivo, glycerol gradient sedimentation, primary cell analysis Nucleic acids research High 17341462 17576689
2007 HMBA activates PI3K/Akt, leading to phosphorylation of HEXIM1, which causes release of active P-TEFb from the HEXIM1/7SK snRNP complex; a phosphorylation-resistant HEXIM1 mutant blocks HMBA-induced P-TEFb release and HIV transcription activation. PI3K/Akt pathway inhibitors, phosphorylation assays, glycerol gradient sedimentation, chromatin immunoprecipitation, HEXIM1 phosphorylation mutants PLoS pathogens High 17937499
2008 LARP7 is a stable component of the 7SK snRNP while HEXIM1 and P-TEFb are reversibly associated; immunodepletion of LARP7 depletes most 7SK RNA regardless of HEXIM1 or P-TEFb presence; LARP7 knockdown decreases steady-state 7SK levels and increases free P-TEFb. Glycerol gradient sedimentation, immunodepletion, siRNA knockdown, Tat transactivation assays Nucleic acids research High 18281698
2008 Nucleophosmin (NPM) binds HEXIM1 in vitro and in vivo and acts as a negative regulator of HEXIM1; NPM overexpression causes proteasome-mediated degradation of HEXIM1 leading to P-TEFb activation; cytoplasmic NPMc+ mutant (found in AML) sequesters HEXIM1 in the cytoplasm, increasing RNA Pol II transcription. Co-immunoprecipitation, GST pull-down, siRNA knockdown, overexpression, subcellular fractionation, immunofluorescence, proteasome inhibitor experiments Journal of molecular biology High 18371977
2007 hnRNPs A1, A2, Q, and R associate with 7SK RNA; their association increases when P-TEFb-HEXIM1-7SK is dissociated following transcription inhibition or HEXIM1 knockdown; knockdown of hnRNPs A1/A2 attenuates transcription-dependent dissociation of P-TEFb-HEXIM1-7SK complexes, implicating hnRNP-7SK interactions in P-TEFb activation. Mass spectrometry identification, immunoprecipitation, siRNA knockdown, glycerol gradient sedimentation Molecular and cellular biology High 17709395
2010 Release of P-TEFb from the 7SK snRNP by HIV-1 Tat or cellular activator Brd4 is accompanied by a major conformational change in 7SK RNA that blocks re-association of HEXIM1, suggesting that reincorporation of HEXIM1 into the 7SK snRNP is the regulated step of reassembly. In vitro P-TEFb release assay using immunoprecipitated 7SK snRNP (anti-LARP7), glycerol gradient sedimentation, RNA chemical modification (SHAPE/dimethyl sulfate probing) PloS one High 20808803
2010 HEXIM1 binds double-stranded RNA in a sequence-independent manner; upon dsRNA binding, a large conformational change occurs in HEXIM1 that allows recruitment and inhibition of P-TEFb; a significant fraction of HEXIM1 is cytoplasmic and both nuclear and cytoplasmic HEXIM1 is RNA-associated; HEXIM1 co-precipitates with miR-16 but not U6 or U2 snRNAs. In vitro RNA competition assays, subcellular fractionation, immunofluorescence, immunoprecipitation with RT-PCR Nucleic acids research Medium 17395637
2010 NMR and biochemical analysis show that a repeated GAUC motif in the upper part of the 5' hairpin of 7SK is essential for specific HEXIM1 recognition; binding of the HEXIM1 arginine-rich motif (ARM) peptide induces opening of the GAUC motif and stabilization of an internal loop; a conserved proline-serine sequence in the ARM is essential for binding specificity and RNA conformational change. NMR spectroscopy, gel-shift assays, mutagenesis of 7SK and HEXIM1 ARM peptide Nucleic acids research High 20675720
2009 Photo-cross-linking identifies U30 of 7SK RNA as contacting HEXIM1 amino acids 210-220 in both a minimal RNA-binding site and a fully reconstituted 7SK/HEXIM1/P-TEFb complex; a minimal 7SK hairpin (nucleotides 24-87) can bind specifically to HEXIM1 in vivo. 4-thioU photo-cross-linking, mass spectrometry, in vivo HEXIM1 binding assays Journal of molecular biology High 19244621
2009 Cyclin T1 preferentially binds HEXIM1 and cyclin T2 preferentially binds HEXIM2 (higher affinities measured by ITC); importin alpha binds HEXIM1 and HEXIM2 to support nuclear import of cyclin T; the 7SK snRNA 5' hairpin (nucleotides 23-88) binds Cyclin T1-HEXIM1 with Kd <0.3 µM. Isothermal titration calorimetry, electrophoretic mobility shift assays, radioactively labelled 7SK snRNA Journal of molecular biology High 19883659
2012 PKC phosphorylates HEXIM1 at serine 158 (S158); phosphorylated HEXIM1 neither binds 7SK snRNA nor inhibits P-TEFb; phorbol esters, T cell antigen receptor engagement, and constitutively active PKCθ all inhibit 7SK snRNP formation and increase P-TEFb-dependent transcription through this mechanism; phosphorylation-resistant HEXIM1 (S158A) blocks these effects. In vitro phosphorylation assay, phosphorylation-resistant mutants, immunoprecipitation, T cell activation assays, glycerol gradient sedimentation Nucleic acids research High 22821562
2005 HEXIM1 forms a distinct complex with glucocorticoid receptor (GR) independently of 7SK RNA, CDK9, or cyclin T1; the arginine-rich NLS of HEXIM1 directly associates with the ligand-binding domain of GR; HEXIM1 overexpression decreases ligand-dependent association between GR and the coactivator TIF2; disruption of 7SK blunted HEXIM1's negative effect on AhR-dependent but not GR-mediated transcription. Co-immunoprecipitation, adenovirus-mediated overexpression, siRNA knockdown, immunofluorescence, domain mapping Proceedings of the National Academy of Sciences of the United States of America High 15941832
2008 HEXIM1 inhibits estrogen receptor alpha (ERα)-mediated transcription by bridging an ERα-P-TEFb interaction; increased HEXIM1 expression in MCF-7 cells and MMTV/HEXIM1 mice decreased estrogen-driven cyclin D1 expression and reduced ERα, P-TEFb, and S2P RNAPII recruitment to ERα-responsive gene promoters; HEXIM1 specifically decreased estrogen-induced P-TEFb activity. ChIP assays, MMTV/HEXIM1 transgenic mouse model, siRNA knockdown, mammary gland functional assays, in vitro kinase assays Cancer research High 18757415
2017 HEXIM1 forms a ribonuclear complex (HDP-RNP) with the lncRNA NEAT1, DNA-PK subunits (DNAPKc, Ku70, Ku80), and paraspeckle proteins (SFPQ, NONO, PSPC1, RBM14, MATRIN3); HEXIM1 binding to NEAT1 is required for HDP-RNP assembly; the HDP-RNP is required for innate immune response to foreign DNA via the cGAS-STING-IRF3 pathway; foreign DNA remodels HDP-RNP to release paraspeckle proteins and recruit STING, activating DNAPKc and IRF3. Immunoprecipitation, mass spectrometry, RNA sequencing, siRNA knockdown, cGAS-STING pathway activation assays Molecular cell High 28712728
2015 PPM1G phosphatase directly binds 7SK RNA and HEXIM1 after P-TEFb has been released from the 7SK snRNP; this dual binding blocks P-TEFb reassembly onto the snRNP to sustain NF-κB-mediated transcription elongation; ATM kinase regulates PPM1G-7SK snRNP interaction through site-specific PPM1G phosphorylation. ChIP assays, in vitro binding assays (direct PPM1G-7SK and PPM1G-HEXIM1 binding), siRNA knockdown, ATM inhibition experiments Molecular and cellular biology High 26324325
2016 Under nucleotide stress, HEXIM1 is induced to form an inhibitory complex with P-TEFb to inhibit elongation at tumorigenic genes in melanoma; HEXIM1 overexpression suppresses melanoma formation in zebrafish while HEXIM1 inactivation accelerates tumor onset; anti-tumorigenic RNAs bind to and are stabilized by HEXIM1 under nucleotide stress. Zebrafish melanoma model (gain- and loss-of-function), human melanoma cell knockdown, RNA immunoprecipitation, gene expression analysis Molecular cell High 27058786
2014 Release of P-TEFb from the 7SK snRNP leads to increased transcription specifically from a proximal (unannotated) HEXIM1 promoter, not the distal promoter; this involves poised RNA Pol II, and the superelongation complex subunits AFF4 and ELL2 are recruited to this proximal promoter after P-TEFb release and are required for its transcriptional effects, creating an autoregulatory feedback loop. ChIP-seq, luciferase reporter assays, P-TEFb-releasing compound treatments, siRNA knockdown of AFF4/ELL2 The Journal of biological chemistry High 24515107
2004 CLP-1 (mouse HEXIM1 ortholog) gene knockout causes prenatal lethality with left ventricular hypertrophy and downregulation of HAND1; CLP-1 null fetal hearts show altered nuclear and myofibril morphologies and re-expression of hypertrophic contractile genes. Gene knockout in mice, electron microscopy, Northern blot, cardiac phenotype analysis Mechanisms of development High 15172687
2007 Insertional mutation disrupting the HEXIM1 C-terminal region causes prenatal lethality with defects in coronary patterning, thin ventricular walls, decreased myocardial vascularization, increased apoptosis, decreased VEGF expression (a direct transcriptional target of HEXIM1), and decreased FGF9; HEXIM1 attenuates repressive effects of C/EBPα on VEGF gene transcription. Insertional gene mutation in mice, PECAM-1 staining, immunohistochemistry, qRT-PCR, ChIP Circulation research High 18079413
2007 CLP-1 (HEXIM1) dissociates from P-TEFb complex under hypertrophic stimuli (mechanical stretch, endothelin-1, phenylephrine) in cardiomyocytes; this dissociation is blocked by JAK2 inhibitor AG490, placing JAK/STAT signaling upstream of CLP-1 release from P-TEFb during cardiac hypertrophy. Immunoprecipitation in primary cardiomyocytes, mechanical stretch assay, JAK2 inhibitor (AG490), immunofluorescence co-localization Cardiovascular research High 17459355
2012 HEXIM1 acts as a positive regulator of p53 by interacting with p53 (C-terminal regions of both proteins required) and preventing HDM2-mediated ubiquitination of p53, thereby enhancing p53 protein stability and upregulating p53 target genes (Puma, p21); HEXIM1 knockdown inhibits p53 induction and prevents cell cycle arrest caused by p53. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, overexpression, cell cycle analysis, target gene expression The Journal of biological chemistry High 22948151
2018 BET inhibition (BRD4 inhibition) releases P-TEFb from its inhibitor HEXIM1, causing a rapid overall increase in RNA synthesis that promotes transcription-replication conflicts; HEXIM1 and RAD51 both promote BET inhibitor-induced fork slowing but prevent a DNA damage response at these conflicts. siRNA knockdown of HEXIM1, DNA fiber assays for fork speed, γH2AX assays for DNA damage, RAD51 foci analysis Cell reports High 30463005
2019 The histone demethylase KDM5B directly represses HEXIM1 expression by occupying the HEXIM1 promoter (H3K4me3/2 demethylation); RNAi knockdown of KDM5B or KDM5B inhibitors induce HEXIM1 expression, inhibit cancer cell proliferation, induce differentiation, and inhibit breast tumor metastasis. Chemical proteomics, biotin-NeutrAvidin pull-down, surface plasmon resonance, ChIP assays, shRNA knockdown, mouse metastasis model Breast cancer research High 31805991
2016 Hexim1 F208 (within the conserved PYNT/202PYNTTQFLM210 sequence) directly contacts the CDK9 activation segment controlling access to the catalytic cleft; reciprocally, Cdk9 W193 cross-links to Hexim1; this contact is proposed to block substrate binding to CDK9, explaining the mechanism of kinase inhibition. Site-specific incorporation of photoreactive amino acids, photo-cross-linking in live cells and in vitro, mass spectrometry Proceedings of the National Academy of Sciences of the United States of America High 27791144

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Edg-1, the G protein-coupled receptor for sphingosine-1-phosphate, is essential for vascular maturation. The Journal of clinical investigation 977 11032855
1998 Sphingosine-1-phosphate as a ligand for the G protein-coupled receptor EDG-1. Science (New York, N.Y.) 853 9488656
1998 Dual actions of sphingosine-1-phosphate: extracellular through the Gi-coupled receptor Edg-1 and intracellular to regulate proliferation and survival. The Journal of cell biology 427 9660876
2003 Inhibition of P-TEFb (CDK9/Cyclin T) kinase and RNA polymerase II transcription by the coordinated actions of HEXIM1 and 7SK snRNA. Molecular cell 404 14580347
2001 Role of the sphingosine-1-phosphate receptor EDG-1 in PDGF-induced cell motility. Science (New York, N.Y.) 369 11230698
1999 Differential coupling of the sphingosine 1-phosphate receptors Edg-1, Edg-3, and H218/Edg-5 to the G(i), G(q), and G(12) families of heterotrimeric G proteins. The Journal of biological chemistry 289 10488065
2000 Inhibitory regulation of Rac activation, membrane ruffling, and cell migration by the G protein-coupled sphingosine-1-phosphate receptor EDG5 but not EDG1 or EDG3. Molecular and cellular biology 275 11094076
2004 Binding of the 7SK snRNA turns the HEXIM1 protein into a P-TEFb (CDK9/cyclin T) inhibitor. The EMBO journal 266 15201869
2001 Akt-mediated phosphorylation of the G protein-coupled receptor EDG-1 is required for endothelial cell chemotaxis. Molecular cell 264 11583630
2001 Sphingosine 1-phosphate-induced endothelial cell migration requires the expression of EDG-1 and EDG-3 receptors and Rho-dependent activation of alpha vbeta3- and beta1-containing integrins. The Journal of biological chemistry 255 11150298
1998 EDG1 is a functional sphingosine-1-phosphate receptor that is linked via a Gi/o to multiple signaling pathways, including phospholipase C activation, Ca2+ mobilization, Ras-mitogen-activated protein kinase activation, and adenylate cyclase inhibition. The Journal of biological chemistry 245 9765227
1998 Sphingosine 1-phosphate signalling through the G-protein-coupled receptor Edg-1. The Biochemical journal 233 9480864
1999 Differential pharmacological properties and signal transduction of the sphingosine 1-phosphate receptors EDG-1, EDG-3, and EDG-5. The Journal of biological chemistry 225 10383399
2003 MAQ1 and 7SK RNA interact with CDK9/cyclin T complexes in a transcription-dependent manner. Molecular and cellular biology 211 12832472
2008 LARP7 is a stable component of the 7SK snRNP while P-TEFb, HEXIM1 and hnRNP A1 are reversibly associated. Nucleic acids research 207 18281698
2000 Sphingosine 1-phosphate stimulates proliferation and migration of human endothelial cells possibly through the lipid receptors, Edg-1 and Edg-3. The Biochemical journal 197 10794715
2017 HEXIM1 and NEAT1 Long Non-coding RNA Form a Multi-subunit Complex that Regulates DNA-Mediated Innate Immune Response. Molecular cell 191 28712728
2007 HMBA releases P-TEFb from HEXIM1 and 7SK snRNA via PI3K/Akt and activates HIV transcription. PLoS pathogens 187 17937499
1983 Repeated DNA sequences upstream from HIS1 also occur at several other co-regulated genes in Saccharomyces cerevisiae. The Journal of biological chemistry 186 6300123
2005 Analysis of the large inactive P-TEFb complex indicates that it contains one 7SK molecule, a dimer of HEXIM1 or HEXIM2, and two P-TEFb molecules containing Cdk9 phosphorylated at threonine 186. The Journal of biological chemistry 183 15965233
1999 Ligand-induced trafficking of the sphingosine-1-phosphate receptor EDG-1. Molecular biology of the cell 169 10198065
2007 Tat competes with HEXIM1 to increase the active pool of P-TEFb for HIV-1 transcription. Nucleic acids research 165 17341462
1996 The inducible G protein-coupled receptor edg-1 signals via the G(i)/mitogen-activated protein kinase pathway. The Journal of biological chemistry 153 8626678
2001 Role of the sphingosine 1-phosphate receptor EDG-1 in vascular smooth muscle cell proliferation and migration. Circulation research 147 11557736
1999 EDG3 is a functional receptor specific for sphingosine 1-phosphate and sphingosylphosphorylcholine with signaling characteristics distinct from EDG1 and AGR16. Biochemical and biophysical research communications 142 10381367
2001 EDG-1 links the PDGF receptor to Src and focal adhesion kinase activation leading to lamellipodia formation and cell migration. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 140 11726541
2000 Agonist-modulated targeting of the EDG-1 receptor to plasmalemmal caveolae. eNOS activation by sphingosine 1-phosphate and the role of caveolin-1 in sphingolipid signal transduction. The Journal of biological chemistry 133 10921915
2000 Identification of Edg1 receptor residues that recognize sphingosine 1-phosphate. The Journal of biological chemistry 133 10982820
2007 Manipulation of P-TEFb control machinery by HIV: recruitment of P-TEFb from the large form by Tat and binding of HEXIM1 to TAR. Nucleic acids research 132 17576689
2006 His1 and His2 are distantly related, spindle-shaped haloviruses belonging to the novel virus group, Salterprovirus. Virology 114 16530800
2004 A human immunodeficiency virus type 1 Tat-like arginine-rich RNA-binding domain is essential for HEXIM1 to inhibit RNA polymerase II transcription through 7SK snRNA-mediated inactivation of P-TEFb. Molecular and cellular biology 113 15169877
1989 Biological activities of des-His1[Glu9]glucagon amide, a glucagon antagonist. Peptides 112 2560175
1998 Lysophosphatidic acid stimulates the G-protein-coupled receptor EDG-1 as a low affinity agonist. The Journal of biological chemistry 107 9705355
2006 Regulation of polymerase II transcription by 7SK snRNA: two distinct RNA elements direct P-TEFb and HEXIM1 binding. Molecular and cellular biology 105 16382153
2005 HEXIM2, a HEXIM1-related protein, regulates positive transcription elongation factor b through association with 7SK. The Journal of biological chemistry 102 15713662
2005 Identification of a cyclin T-binding domain in Hexim1 and biochemical analysis of its binding competition with HIV-1 Tat. The Journal of biological chemistry 102 15855166
2010 The mechanism of release of P-TEFb and HEXIM1 from the 7SK snRNP by viral and cellular activators includes a conformational change in 7SK. PloS one 94 20808803
2007 The transcription-dependent dissociation of P-TEFb-HEXIM1-7SK RNA relies upon formation of hnRNP-7SK RNA complexes. Molecular and cellular biology 93 17709395
2011 Sphingosine kinase 1 promotes tumour cell migration and invasion via the S1P/EDG1 axis in hepatocellular carcinoma. Liver international : official journal of the International Association for the Study of the Liver 89 22098666
2005 Compensatory contributions of HEXIM1 and HEXIM2 in maintaining the balance of active and inactive positive transcription elongation factor b complexes for control of transcription. The Journal of biological chemistry 89 15713661
2005 Interplay between 7SK snRNA and oppositely charged regions in HEXIM1 direct the inhibition of P-TEFb. The EMBO journal 89 16362050
2001 A single amino acid determines lysophospholipid specificity of the S1P1 (EDG1) and LPA1 (EDG2) phospholipid growth factor receptors. The Journal of biological chemistry 89 11604399
2001 EDG1 receptor stimulation leads to cardiac hypertrophy in rat neonatal myocytes. Journal of molecular and cellular cardiology 83 11549339
1998 His1, an archaeal virus of the Fuselloviridae family that infects Haloarcula hispanica. Journal of virology 82 9765495
1989 Histatins, a family of salivary histidine-rich proteins, are encoded by at least two loci (HIS1 and HIS2). Biochemical and biophysical research communications 77 2719677
2001 Dual regulation of EDG1/S1P(1) receptor phosphorylation and internalization by protein kinase C and G-protein-coupled receptor kinase 2. The Journal of biological chemistry 76 11741892
2001 Sphingosine 1-phosphate activates nuclear factor-kappa B through Edg receptors. Activation through Edg-3 and Edg-5, but not Edg-1, in human embryonic kidney 293 cells. The Journal of biological chemistry 69 11673450
2016 Stress from Nucleotide Depletion Activates the Transcriptional Regulator HEXIM1 to Suppress Melanoma. Molecular cell 66 27058786
2014 Brd4 and HEXIM1: multiple roles in P-TEFb regulation and cancer. BioMed research international 65 24592384
2002 N-glycans of sphingosine 1-phosphate receptor Edg-1 regulate ligand-induced receptor internalization. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 65 12087059
1997 The mouse gene for the inducible G-protein-coupled receptor edg-1. Genomics 65 9226368
2005 Oligomerization of HEXIM1 via 7SK snRNA and coiled-coil region directs the inhibition of P-TEFb. Nucleic acids research 62 16377779
2000 Sphingosine 1-phosphate: a ligand for the EDG-1 family of G-protein-coupled receptors. Annals of the New York Academy of Sciences 56 10818441
2007 Structure of the Cyclin T binding domain of Hexim1 and molecular basis for its recognition of P-TEFb. Proceedings of the National Academy of Sciences of the United States of America 55 17724342
2004 Ablation of the CLP-1 gene leads to down-regulation of the HAND1 gene and abnormality of the left ventricle of the heart and fetal death. Mechanisms of development 55 15172687
2016 HEXIM1 as a Robust Pharmacodynamic Marker for Monitoring Target Engagement of BET Family Bromodomain Inhibitors in Tumors and Surrogate Tissues. Molecular cancer therapeutics 54 27903752
2004 Atypical cannabinoid stimulates endothelial cell migration via a Gi/Go-coupled receptor distinct from CB1, CB2 or EDG-1. European journal of pharmacology 51 15063151
2008 Nucleophosmin interacts with HEXIM1 and regulates RNA polymerase II transcription. Journal of molecular biology 49 18371977
2014 Release of positive transcription elongation factor b (P-TEFb) from 7SK small nuclear ribonucleoprotein (snRNP) activates hexamethylene bisacetamide-inducible protein (HEXIM1) transcription. The Journal of biological chemistry 48 24515107
2012 PKC phosphorylates HEXIM1 and regulates P-TEFb activity. Nucleic acids research 48 22821562
2007 HEXIM1 and the control of transcription elongation: from cancer and inflammation to AIDS and cardiac hypertrophy. Cell cycle (Georgetown, Tex.) 47 17671421
2000 Expression and characterization of Edg-1 receptors in rat cardiomyocytes: calcium deregulation in response to sphingosine 1-phosphate. European journal of biochemistry 47 10971577
2008 beta-Arrestin recruitment assay for the identification of agonists of the sphingosine 1-phosphate receptor EDG1. Journal of biomolecular screening 45 19036707
2012 Modified coat protein forms the flexible spindle-shaped virion of haloarchaeal virus His1. Environmental microbiology 44 23163639
2007 HEXIM1 is a promiscuous double-stranded RNA-binding protein and interacts with RNAs in addition to 7SK in cultured cells. Nucleic acids research 43 17395637
2016 An evolutionary conserved Hexim1 peptide binds to the Cdk9 catalytic site to inhibit P-TEFb. Proceedings of the National Academy of Sciences of the United States of America 42 27791144
2000 Sphingosine-1-phosphate signaling via the EDG-1 family of G-protein-coupled receptors. Annals of the New York Academy of Sciences 42 10818438
2000 Differential roles of Edg-1 and Edg-5, sphingosine 1-phosphate receptors, in the signaling pathways in C6 glioma cells. Brain research. Molecular brain research 42 11146117
2018 BET Inhibition Induces HEXIM1- and RAD51-Dependent Conflicts between Transcription and Replication. Cell reports 41 30463005
2015 PPM1G Binds 7SK RNA and Hexim1 To Block P-TEFb Assembly into the 7SK snRNP and Sustain Transcription Elongation. Molecular and cellular biology 41 26324325
2001 The sphingosine-1-phosphate receptor EDG-1 is essential for platelet-derived growth factor-induced cell motility. Biochemical Society transactions 41 11709084
1993 Nucleotide sequence analysis of the human salivary protein genes HIS1 and HIS2, and evolution of the STATH/HIS gene family. Molecular biology and evolution 41 8336540
1995 Cloning of the Candida albicans HIS1 gene by direct complementation of a C. albicans histidine auxotroph using an improved double-ARS shuttle vector. Gene 40 7489899
1994 Retroviral insertions in the murine His-1 locus activate the expression of a novel RNA that lacks an extensive open reading frame. Molecular and cellular biology 40 8114708
2022 Linker histone variant HIS1-3 and WRKY1 oppositely regulate salt stress tolerance in Arabidopsis. Plant physiology 39 35474141
2005 HEXIM1 forms a transcriptionally abortive complex with glucocorticoid receptor without involving 7SK RNA and positive transcription elongation factor b. Proceedings of the National Academy of Sciences of the United States of America 39 15941832
2010 HEXIM1 targets a repeated GAUC motif in the riboregulator of transcription 7SK and promotes base pair rearrangements. Nucleic acids research 38 20675720
2010 T-loop phosphorylated Cdk9 localizes to nuclear speckle domains which may serve as sites of active P-TEFb function and exchange between the Brd4 and 7SK/HEXIM1 regulatory complexes. Journal of cellular physiology 37 20201073
1991 His-1 and His-2: identification and chromosomal mapping of two commonly rearranged sites of viral integration in a myeloid leukemia. Oncogene 35 1682866
2005 Inhibition of Tat activity by the HEXIM1 protein. Retrovirology 34 15992410
2007 Mutation of the HEXIM1 gene results in defects during heart and vascular development partly through downregulation of vascular endothelial growth factor. Circulation research 33 18079413
2006 Increased HEXIM1 expression during erythroleukemia and neuroblastoma cell differentiation. Journal of cellular physiology 33 16222702
1994 Cloning of the rat edg-1 immediate-early gene: expression pattern suggests diverse functions. Gene 31 7959012
2012 Inhibition of metastasis by HEXIM1 through effects on cell invasion and angiogenesis. Oncogene 30 22964639
2008 HEXIM1 regulates 17beta-estradiol/estrogen receptor-alpha-mediated expression of cyclin D1 in mammary cells via modulation of P-TEFb. Cancer research 30 18757415
2005 Cloning and disruption of the Pichia pastoris ARG1, ARG2, ARG3, HIS1, HIS2, HIS5, HIS6 genes and their use as auxotrophic markers. Yeast (Chichester, England) 29 15789348
2012 Identification of HEXIM1 as a positive regulator of p53. The Journal of biological chemistry 27 22948151
2010 HEXIM1 modulates vascular endothelial growth factor expression and function in breast epithelial cells and mammary gland. Oncogene 27 20453883
2007 Pivotal role of cardiac lineage protein-1 (CLP-1) in transcriptional elongation factor P-TEFb complex formation in cardiac hypertrophy. Cardiovascular research 27 17459355
2002 Structure, expression, and functional characterization of the mouse CLP-1 gene. Gene 27 12119119
2012 CCR7/CCL19 controls expression of EDG-1 in T cells. The Journal of biological chemistry 26 22334704
2009 Specificity of Hexim1 and Hexim2 complex formation with cyclin T1/T2, importin alpha and 7SK snRNA. Journal of molecular biology 26 19883659
2019 Inhibition of the histone demethylase, KDM5B, directly induces re-expression of tumor suppressor protein HEXIM1 in cancer cells. Breast cancer research : BCR 25 31805991
1993 Mechanism of action of des-His1-[Glu9]glucagon amide, a peptide antagonist of the glucagon receptor system. Proceedings of the National Academy of Sciences of the United States of America 22 8383321
1981 Marker effects and the nature of the recombination event at the his1 locus of Saccharomyces cerevisiae. Current genetics 22 24189951
2012 Cardiac lineage protein-1 (CLP-1) regulates cardiac remodeling via transcriptional modulation of diverse hypertrophic and fibrotic responses and angiotensin II-transforming growth factor β (TGF-β1) signaling axis. The Journal of biological chemistry 21 22308025
2007 Inhibiting lentiviral replication by HEXIM1, a cellular negative regulator of the CDK9/cyclin T complex. AIDS (London, England) 21 17314519
2018 Hexim1, an RNA-controlled protein hub. Transcription 20 29345523
2010 Human T-lymphotropic virus type 1 Tax protein complexes with P-TEFb and competes for Brd4 and 7SK snRNP/HEXIM1 binding. Journal of virology 20 20926576
2009 U30 of 7SK RNA forms a specific photo-cross-link with Hexim1 in the context of both a minimal RNA-binding site and a fully reconstituted 7SK/Hexim1/P-TEFb ribonucleoprotein complex. Journal of molecular biology 20 19244621