Evidence map›Paper›PMID 38671004›Full record

ArticleNature communications2024

Diphthamide deficiency promotes association of eEF2 with p53 to induce p21 expression and neural crest defects.

Yu Shi, Daochao Huang, Cui Song, Ruixue Cao, Zhao Wang, Dan Wang, Li Zhao, Xiaolu Xu, Congyu Lu, Feng Xiong and 13 more

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

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
1.6field-weighted citation impact, top 19% 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

3 citing papers in PubMed, 4 citations in OpenAlex.

  1. Article
  2. Review
  3. 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

23 authors at 5 institutions in 2 countries.

Yu Shi *Department of Clinical Laboratory, Children's Hospital of Chongqing Medical University, Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, 136 Zhongshan 2nd Rd, Chongqing, 400014, China. shiyu@hospital.cqmu.edu.cn.ORCID http://orcid.org/0009-0007-2426-0113
Daochao Huang *Department of Pediatric Research Institute, Children's Hospital of Chongqing Medical University, 136 Zhongshan 2nd Rd, Chongqing, 400014, China.
Cui Song *Department of Endocrinology and Genetic Metabolism Disease, Children's Hospital of Chongqing Medical University, 136 Zhongshan 2nd Rd, Chongqing, 400014, China.
Ruixue CaoOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Institute of Aging, Key Laboratory of Alzheimer's Disease of Zhejiang Province, School of Mental Health and Kangning Hospital, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China.
Zhao WangOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Institute of Aging, Key Laboratory of Alzheimer's Disease of Zhejiang Province, School of Mental Health and Kangning Hospital, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China.ORCID http://orcid.org/0000-0002-2491-5075
Dan WangDepartment of Pediatric Research Institute, Children's Hospital of Chongqing Medical University, 136 Zhongshan 2nd Rd, Chongqing, 400014, China.
Li ZhaoDepartment of Pediatric Research Institute, Children's Hospital of Chongqing Medical University, 136 Zhongshan 2nd Rd, Chongqing, 400014, China.
Xiaolu XuDepartment of Biological Sciences, University of Delaware, Newark, DE, 19716, USA.
Congyu LuDepartment of Biological Sciences, University of Delaware, Newark, DE, 19716, USA.
Feng XiongDepartment of Endocrinology and Genetic Metabolism Disease, Children's Hospital of Chongqing Medical University, 136 Zhongshan 2nd Rd, Chongqing, 400014, China.
Haowen ZhaoDepartment of Clinical Laboratory, Children's Hospital of Chongqing Medical University, Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, 136 Zhongshan 2nd Rd, Chongqing, 400014, China.
Shuxiang LiDepartment of Pediatric Research Institute, Children's Hospital of Chongqing Medical University, 136 Zhongshan 2nd Rd, Chongqing, 400014, China.
Quansheng ZhouDepartment of Pediatric Research Institute, Children's Hospital of Chongqing Medical University, 136 Zhongshan 2nd Rd, Chongqing, 400014, China.
Shuyue LuoDepartment of Pediatric Research Institute, Children's Hospital of Chongqing Medical University, 136 Zhongshan 2nd Rd, Chongqing, 400014, China.
Dongjie HuDepartment of Pediatric Research Institute, Children's Hospital of Chongqing Medical University, 136 Zhongshan 2nd Rd, Chongqing, 400014, China.
Yun ZhangDepartment of Radiology, Children's Hospital of Chongqing Medical University, 136 Zhongshan 2nd Rd, Chongqing, 400014, China.
Cui WangDepartment of Radiology, Children's Hospital of Chongqing Medical University, 136 Zhongshan 2nd Rd, Chongqing, 400014, China.
Yiping ShenDivision of Genetics and Genomics, Boston Children's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
Weiting SuKunming Institute of Zoology, Chinese Academy of Science, Kunming, 650223, Yunnan, China.
Yili WuOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Institute of Aging, Key Laboratory of Alzheimer's Disease of Zhejiang Province, School of Mental Health and Kangning Hospital, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China.
Karl SchmitzDepartment of Biological Sciences, University of Delaware, Newark, DE, 19716, USA.ORCID http://orcid.org/0000-0003-1411-7624
Shuo WeiDepartment of Biological Sciences, University of Delaware, Newark, DE, 19716, USA. swei@udel.edu.ORCID http://orcid.org/0000-0001-8203-4922
Weihong SongOujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Institute of Aging, Key Laboratory of Alzheimer's Disease of Zhejiang Province, School of Mental Health and Kangning Hospital, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China. weihong@wmu.edu.cn.ORCID http://orcid.org/0000-0001-9928-889X
Children's Hospital of Chongqing Medical University · CNUniversity of Delaware · USWenzhou Medical University · CNBoston Children's Hospital · USKunming Institute of Zoology · CN

Funding

Mechanisms of Neural Crest Induction and Craniofacial DisordersR01DE029802 · NIDCR · UNIVERSITY OF DELAWARE · PI WEI, SHUO · 2020 to 2024
$1.8M
NIDCR NIH HHS R01 DE029802
6 · The paper itself

Abstract

Diphthamide is a modified histidine residue unique for eukaryotic translation elongation factor 2 (eEF2), a key ribosomal protein. Loss of this evolutionarily conserved modification causes developmental defects through unknown mechanisms. In a patient with compound heterozygous mutations in Diphthamide Biosynthesis 1 (DPH1) and impaired eEF2 diphthamide modification, we observe multiple defects in neural crest (NC)-derived tissues. Knockin mice harboring the patient's mutations and Xenopus embryos with Dph1 depleted also display NC defects, which can be attributed to reduced proliferation in the neuroepithelium. DPH1 depletion facilitates dissociation of eEF2 from ribosomes and association with p53 to promote transcription of the cell cycle inhibitor p21, resulting in inhibited proliferation. Knockout of one p21 allele rescues the NC phenotypes in the knockin mice carrying the patient's mutations. These findings uncover an unexpected role for eEF2 as a transcriptional coactivator for p53 to induce p21 expression and NC defects, which is regulated by diphthamide modification.

Indexed as

Cyclin-Dependent Kinase Inhibitor p21HistidineMinor Histocompatibility AntigensNeural CrestPeptide Elongation Factor 2Tumor Suppressor Protein p53Tumor Suppressor ProteinsAnimalsCell ProliferationFemaleGene Knock-In TechniquesHumansMaleMiceMice, KnockoutMutationCDKN1A protein, humanCyclin-Dependent Kinase Inhibitor p21diphthamideDPH1 protein, humanHistidineMinor Histocompatibility AntigensPeptide Elongation Factor 2TP53 protein, humanTumor Suppressor Protein p53Tumor Suppressor Proteins

Identifiers

PMID38671004
PMCPMC11053169
OpenAlexW4395668182

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.