Evidence map›Paper›PMID 10866664›Full record

ArticleMolecular and cellular biology2000

Tat modifies the activity of CDK9 to phosphorylate serine 5 of the RNA polymerase II carboxyl-terminal domain during human immunodeficiency virus type 1 transcription.

M Zhou, M A Halanski, M F Radonovich, F Kashanchi, J Peng, D H Price, J N Brady

Open access · greenAbstract read
In one paragraph

Article in Molecular and cellular biology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 132 papers.

0numbers the graph read from it
0cells of the map it votes in
132citing papers in PubMed
6.8field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

132 citing papers in PubMed, 261 citations in OpenAlex.

  1. HIV-1 latency: From acquaintance to confidant.Journal of virus eradication · 2025
    Review
  2. Article
  3. Review
  4. Review
  5. Review
  6. Article
  7. Article
  8. HIV-1 Transcription Inhibition Using Small RNA-Binding Molecules.Pharmaceuticals (Basel, Switzerland) · 2023
    Article
  9. Article
  10. Review
  11. Review
  12. Article
  13. Review
  14. Review
  15. JMJD5 couples with CDK9 to release the paused RNA polymerase II.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  16. Review
  17. P-TEFb as A Promising Therapeutic Target.Molecules (Basel, Switzerland) · 2020
    Review
  18. Review
  19. Article
  20. Review

72 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

M ZhouVirus Tumor Biology Section, LRBGE, Division of Basic Sciences, National Cancer Institute, Bethesda, Maryland 20892, USA.
M A Halanski
M F Radonovich
F Kashanchi
J Peng
D H Price
J N Brady
National Cancer Institute · US

Funding

HIV Tat Transcriptional Activation Z01BC005753 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI BRADY, JOHN N. · 1996 to 2008
$714k
HIV Tat Transcriptional ActivationZIABC005753 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI BRADY, JOHN N. · 2009 to 2009
$355k
6 · The paper itself

Abstract

Tat stimulates human immunodeficiency virus type 1 (HIV-1) transcriptional elongation by recruitment of carboxyl-terminal domain (CTD) kinases to the HIV-1 promoter. Using an immobilized DNA template assay, we have analyzed the effect of Tat on kinase activity during the initiation and elongation phases of HIV-1 transcription. Our results demonstrate that cyclin-dependent kinase 7 (CDK7) (TFIIH) and CDK9 (P-TEFb) both associate with the HIV-1 preinitiation complex. Hyperphosphorylation of the RNA polymerase II (RNAP II) CTD in the HIV-1 preinitiation complex, in the absence of Tat, takes place at CTD serine 2 and serine 5. Analysis of preinitiation complexes formed in immunodepleted extracts suggests that CDK9 phosphorylates serine 2, while CDK7 phosphorylates serine 5. Remarkably, in the presence of Tat, the substrate specificity of CDK9 is altered, such that the kinase phosphorylates both serine 2 and serine 5. Tat-induced CTD phosphorylation by CDK9 is strongly inhibited by low concentrations of 5, 6-dichloro-1-beta-D-ribofuranosylbenzimidazole, an inhibitor of transcription elongation by RNAP II. Analysis of stalled transcription elongation complexes demonstrates that CDK7 is released from the transcription complex between positions +14 and +36, prior to the synthesis of transactivation response (TAR) RNA. In contrast, CDK9 stays associated with the complex through +79. Analysis of CTD phosphorylation indicates a biphasic modification pattern, one in the preinitiation complex and the other between +36 and +79. The second phase of CTD phosphorylation is Tat-dependent and TAR-dependent. These studies suggest that the ability of Tat to increase transcriptional elongation may be due to its ability to modify the substrate specificity of the CDK9 complex.

Indexed as

Transcription, GeneticBiotinCyclin-Dependent Kinase 9Cyclin-Dependent Kinase-Activating KinaseCyclin-Dependent KinasesDichlororibofuranosylbenzimidazoleEnzyme InhibitorsGene Products, tatHIV-1HIV Long Terminal RepeatHumansPhosphorylationPositive Transcriptional Elongation Factor BProtein Serine-Threonine KinasesRecombinant ProteinsRNA Polymerase IIBiotinCDK9 protein, humanCyclin-Dependent Kinase 9Cyclin-Dependent Kinase-Activating KinaseCyclin-Dependent KinasesDichlororibofuranosylbenzimidazoleEnzyme InhibitorsGene Products, tatPositive Transcriptional Elongation Factor BProtein Serine-Threonine KinasesRecombinant ProteinsRNA Polymerase IISerinetat Gene Products, Human Immunodeficiency Virus

Identifiers

PMID10866664
PMCPMC85957
OpenAlexW2169963834

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.