Evidence map›Paper›PMID 31135261›Full record

ArticleTranscription2019

PML-RARα induces all-trans retinoic acid-dependent transcriptional activation through interaction with MED1.

Tomoya Fukuoka, Asami Kawai, Taku Takahara, Mahiro Mori, Robert G Roeder, Natsumi Hasegawa, Mitsuhiro Ito

Open access · bronzeAbstract read
In one paragraph

Article in Transcription, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact, top 96% 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

0 citing papers in PubMed, 0 citations in OpenAlex.

No citing paper in PubMed yet.

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 2 institutions in 2 countries.

Tomoya Fukuokaa Laboratory of Hematology, Division of Medical Biophysics , Kobe University Graduate School of Health Sciences , Kobe , Japan.
Asami Kawaia Laboratory of Hematology, Division of Medical Biophysics , Kobe University Graduate School of Health Sciences , Kobe , Japan.
Taku Takaharaa Laboratory of Hematology, Division of Medical Biophysics , Kobe University Graduate School of Health Sciences , Kobe , Japan.
Mahiro Moria Laboratory of Hematology, Division of Medical Biophysics , Kobe University Graduate School of Health Sciences , Kobe , Japan.
Robert G Roederb Laboratory of Biochemistry and Molecular Biology , the Rockefeller University , New York , NY , USA.ORCID 0000-0003-3865-8572
Natsumi Hasegawaa Laboratory of Hematology, Division of Medical Biophysics , Kobe University Graduate School of Health Sciences , Kobe , Japan.
Mitsuhiro Itoa Laboratory of Hematology, Division of Medical Biophysics , Kobe University Graduate School of Health Sciences , Kobe , Japan.
Kobe University · JPRockefeller University · US

Funding

Nuclear Receptor Coactivator Functions and MechanismsR01DK071900 · NIDDK · ROCKEFELLER UNIVERSITY · PI ROEDER, ROBERT G · 2005 to 2015
$5.9M
NIDDK NIH HHS R01 DK071900
6 · The paper itself

Abstract

Transcriptional activation by PML-RARα, an acute promyelocytic leukemia-related oncofusion protein, requires pharmacological concentrations of all-trans retinoic acid (ATRA). However, the mechanism by which the liganded PML-RARα complex leads to the formation of the preinitiation complex has been unidentified. Here we demonstrate that the Mediator subunit MED1 plays an important role in the ATRA-dependent activation of the PML-RARα-bound promoter. Luciferase reporter assays showed that PML-RARα induced significant transcription at pharmacological doses (1 μM) of ATRA; however, this was submaximal and equivalent to the level of transcription driven by intact RARα at physiological doses (1 nM) of ATRA. Transcription depended upon the interaction of PML-RARα with the two LxxLL nuclear receptor recognition motifs of MED1, and LxxLL→LxxAA mutations led to minimal transcription. Mechanistically, MED1 interacted ATRA-dependently with the RARα portion of PML-RARα through the two LxxLL motifs of MED1. These results suggest that PML-RARα initiates ATRA-induced transcription through its interaction with MED1.

Indexed as

HumansMediator Complex Subunit 1Oncogene Proteins, FusionProtein BindingTranscriptional ActivationTretinoinMED1 protein, humanMediator Complex Subunit 1Oncogene Proteins, Fusionpromyelocytic leukemia-retinoic acid receptor alpha fusion oncoproteinTretinoinLxxLL nuclear receptor recognition motifsMED1MediatorPML–RARαtranscriptional activation

Identifiers

PMID31135261
PMCPMC6619921
OpenAlexW2947044354

What OpenQuestion holds

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Read underepoch 390

Registered trials

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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.