Evidence map›Paper›PMID 31796886›Full record

ArticleCell death and differentiation2020

Competitive ubiquitination activates the tumor suppressor p53.

Xingyao Li, Mengqi Guo, Lun Cai, Tingting Du, Ying Liu, Han-Fei Ding, Hongbo Wang, Junran Zhang, Xiaoguang Chen, Chunhong Yan

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death and differentiation, 2020. 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
2.0field-weighted citation impact, top 13% 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, 41 citations in OpenAlex.

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  19. P73 C-terminus is dispensable for multiciliogenesis.Cell cycle (Georgetown, Tex.) · 2020
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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

10 authors at 5 institutions in 2 countries.

Xingyao LiGeorgia Cancer Center, Augusta University, Augusta, GA, 30912, USA.
Mengqi GuoCollege of Pharmacy, Yantai University, Yantai, Shandong, China.
Lun CaiGeorgia Cancer Center, Augusta University, Augusta, GA, 30912, USA.
Tingting DuGeorgia Cancer Center, Augusta University, Augusta, GA, 30912, USA.
Ying LiuDepartment of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100081, China.
Han-Fei DingGeorgia Cancer Center, Augusta University, Augusta, GA, 30912, USA.
Hongbo WangCollege of Pharmacy, Yantai University, Yantai, Shandong, China.
Junran ZhangDepartment of Radiation Oncology, Ohio State University, Columbus, OH, 43210, USA.
Xiaoguang ChenDepartment of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100081, China.
Chunhong YanGeorgia Cancer Center, Augusta University, Augusta, GA, 30912, USA. cyan@augusta.edu.
Augusta University Health · USAugusta University · USChinese Academy of Medical Sciences & Peking Union Medical College · CNYantai University · CNThe Ohio State University · US

Funding

ATF3 Regulation of Histone Acetylation in Genome MaintenanceR01CA240966 · NCI · AUGUSTA UNIVERSITY · PI YAN, CHUNHONG · 2020 to 2025
$1.7M
The Role of ATF3 in the DNA Damage ResponseR01CA139107 · NCI · AUGUSTA UNIVERSITY · PI YAN, CHUNHONG · 2010 to 2015
$1.2M
Screening Assays for Small Molecules Targeting Oncogenic eIF4E ExpressionR01CA164006 · NCI · AUGUSTA UNIVERSITY · PI YAN, CHUNHONG · 2012 to 2014
$832k
NCI NIH HHS R01 CA139107NCI NIH HHS R01 CA164006NCI NIH HHS R01 CA240966
6 · The paper itself

Abstract

Blocking p53 ubiquitination through disrupting its interaction with MDM2 or inhibiting the MDM2 catalytic activity is the central mechanism by which the tumor suppressor p53 is activated in response to genotoxic challenges. Although MDM2 is first characterized as the major E3 ubiquitin ligase for p53, it can also catalyze the conjugation of ubiquitin moieties to other proteins (e.g., activating transcription factor 3, or ATF3). Here we report that ATF3 can act as an ubiquitin "trap" and competes with p53 for MDM2-mediated ubiquitination. While ATF3-mediated p53 stabilization required ATF3 binding to the MDM2 RING domain, we demonstrated that ATF3 ubiquitination catalyzed by MDM2 was indispensable for p53 activation in response to DNA damage. Moreover, a cancer-derived ATF3 mutant (R88G) devoid of ubiquitination failed to prevent p53 from MDM2-mediated degradation and thus was unable to activate the tumor suppressor. Therefore, we have identified a previously-unknown mechanism that can activate p53 in the genotoxic response.

Indexed as

Activating Transcription Factor 3Cell Line, TumorDNA DamageHumansProtein BindingProto-Oncogene Proteins c-mdm2Tumor Suppressor Protein p53UbiquitinationActivating Transcription Factor 3ATF3 protein, humanMDM2 protein, humanProto-Oncogene Proteins c-mdm2TP53 protein, humanTumor Suppressor Protein p53

Identifiers

PMID31796886
PMCPMC7244561
OpenAlexW2991994023

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.