Evidence map›Paper›PMID 38586029›Full record

ArticlebioRxiv : the preprint server for biology2024

p300/CBP degradation is required to disable the active AR enhanceosome in prostate cancer.

Jie Luo, Zhixiang Chen, Yuanyuan Qiao, Jean Ching-Yi Tien, Eleanor Young, Rahul Mannan, Somnath Mahapatra, Tongchen He, Sanjana Eyunni, Yuping Zhang and 14 more

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. 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
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, 10 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

24 authors at 3 institutions in 2 countries.

Jie LuoMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
Zhixiang ChenRogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.
Yuanyuan QiaoMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
Jean Ching-Yi TienMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
Eleanor YoungMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
Rahul MannanMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
Somnath MahapatraMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
Tongchen HeMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
Sanjana EyunniMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
Yuping ZhangMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
Yang ZhengMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
Fengyun SuMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
Xuhong CaoMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
Rui WangMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
Yunhui ChengMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
Rithvik SeriMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
James GeorgeMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
Miriam ShahineMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
Stephanie J MinerMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
Ulka VaishampayanDepartment of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Mi WangRogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.
Shaomeng WangRogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.
Abhijit ParoliaMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
Arul M ChinnaiyanMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0001-9282-3415
University of Michigan · USHoward Hughes Medical Institute · USChinese Academy of Sciences · CN

Funding

Tissue/InformaticsP50CA186786 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Robert Timothy Dess · 2014 to 2026
$27.6M
Exploring Precision Oncology: From Gene Fusions to lncRNAsR35CA231996 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CHINNAIYAN, ARUL M · 2018 to 2024
$6.4M
NCI NIH HHS P50 CA186786NCI NIH HHS R35 CA231996
6 · The paper itself

Abstract

Prostate cancer is an exemplar of an enhancer-binding transcription factor-driven disease. The androgen receptor (AR) enhanceosome complex comprised of chromatin and epigenetic coregulators assembles at enhancer elements to drive disease progression. The paralog lysine acetyltransferases p300 and CBP deposit histone marks that are associated with enhancer activation. Here, we demonstrate that p300/CBP are determinant cofactors of the active AR enhanceosome in prostate cancer. Histone H2B N-terminus multisite lysine acetylation (H2BNTac), which is exclusively reliant on p300/CBP catalytic function, marked active enhancers and was notably elevated in prostate cancer lesions relative to the adjacent benign epithelia. Degradation of p300/CBP rapidly depleted acetylation marks associated with the active AR enhanceosome, which was only partially phenocopied by inhibition of their reader bromodomains. Notably, H2BNTac was effectively abrogated only upon p300/CBP degradation, which led to a stronger suppression of p300/CBP-dependent oncogenic gene programs relative to bromodomain inhibition or the inhibition of its catalytic domain.

Indexed as

androgen receptor enhanceosomeCBPhistone H2BNTacp300p300/CBP degraderprostate cancer

Identifiers

PMID38586029
PMCPMC10996709
OpenAlexW4393354832

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.