Evidence map›Paper›PMID 25492871›Full record

ArticleThe Journal of biological chemistry2015

Visualization of positive transcription elongation factor b (P-TEFb) activation in living cells.

Koh Fujinaga, Zeping Luo, Fred Schaufele, B Matija Peterlin

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.0field-weighted citation impact, top 26% 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

19 citing papers in PubMed, 29 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Latency Reversing Agents: Kick and Kill of HTLV-1?International journal of molecular sciences · 2021
    Review
  6. Article
  7. Article
  8. Review
  9. P-TEFb as A Promising Therapeutic Target.Molecules (Basel, Switzerland) · 2020
    Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Molecular mechanisms of HIV latency.The Journal of clinical investigation · 2016
    Review
  19. Article
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

4 authors at 3 institutions in 4 countries.

Koh FujinagaFrom the Departments of Medicine, Microbiology, and Immunology and.
Zeping LuoFrom the Departments of Medicine, Microbiology, and Immunology and.
Fred Schaufelethe Diabetes and Endocrinology Research Center, University of California, San Francisco, California 94143-0703.
B Matija PeterlinFrom the Departments of Medicine, Microbiology, and Immunology and matija.peterlin@ucsf.edu.
Czech Academy of Sciences, Institute of Microbiology · CZUniversity of California, San Francisco · USUniversity of Mataram · ID

Funding

X-ray Screening and Rapid Structure DeterminationP50GM082250 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FRANKEL, ALAN D · 2007 to 2018
$48.8M
Using NK Cells to eliminate the latent HIV reservoirU19AI096113 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI LUCIW, PAUL · 2011 to 2015
$39.5M
NIAID NIH HHS AI1049104NIAID NIH HHS U19 AI096113NIGMS NIH HHS P50 GM082250
6 · The paper itself

Abstract

Regulation of transcription elongation by positive transcription elongation factor b (P-TEFb) plays a central role in determining the state of cell activation, proliferation, and differentiation. In cells, P-TEFb exists in active and inactive forms. Its release from the inactive 7SK small nuclear ribonucleoprotein complex is a critical step for P-TEFb to activate transcription elongation. However, no good method exists to analyze this P-TEFb equilibrium in living cells. Only inaccurate and labor-intensive cell-free biochemical assays are currently available. In this study, we present the first experimental system to monitor P-TEFb activation in living cells. We created a bimolecular fluorescence complementation assay to detect interactions between P-TEFb and its substrate, the C-terminal domain of RNA polymerase II. When cells were treated with suberoylanilide hydroxamic acid, which releases P-TEFb from the 7SK small nuclear ribonucleoprotein, they turned green. Other known P-TEFb-releasing agents, including histone deacetylase inhibitors, bromodomain and extraterminal bromodomain inhibitors, and protein kinase C agonists, also scored positive in this assay. Finally, we identified 5'-azacytidine as a new P-TEFb-releasing agent. This release of P-TEFb correlated directly with activation of human HIV and HEXIM1 transcription. Thus, our visualization of P-TEFb activation by fluorescent complementation assay could be used to find new P-TEFb-releasing agents, compare different classes of agents, and assess their efficacy singly and/or in combination.

Indexed as

ApoptosisAzacitidineBacterial ProteinsCell-Free SystemGenetic Complementation TestGlycerolHEK293 CellsHeLa CellsHistone Deacetylase InhibitorsHumansHydroxamic AcidsLuminescent ProteinsMicroscopy, FluorescencePlasmidsPositive Transcriptional Elongation Factor BProtein Kinase CAzacitidineBacterial ProteinsGlycerolHistone Deacetylase InhibitorsHydroxamic AcidsLuminescent ProteinsPositive Transcriptional Elongation Factor BProtein Kinase CRibonucleoproteinsRibonucleoproteins, Small NuclearRNA-Binding ProteinsVorinostatyellow fluorescent protein, Bacteria7SK snRNPdrug screeningfluorescencegene transcriptiontranscription elongation factor

Identifiers

PMID25492871
PMCPMC4340424
OpenAlexW1980861325

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.