Evidence map›Paper›PMID 38744853›Full record

ArticleCell death & disease2024

The NTE domain of PTENα/β promotes cancer progression by interacting with WDR5 via its SSSRRSS motif.

Xiaolei Huang, Cheng Zhang, Xinci Shang, Yichang Chen, Qin Xiao, Zhengguo Wei, Guanghui Wang, Xuechu Zhen, Guoqiang Xu, Jinrong Min and 2 more

Abstract read
In one paragraph

Article in Cell death & disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Article
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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

12 authors.

Xiaolei Huang *Jiangsu Key Laboratory of Neuropsychiatric Diseases, Jiangsu Province Engineering Research Center of Precision Diagnostics and Therapeutics Development, College of Pharmaceutical Sciences, Soochow University, 215123, Suzhou, Jiangsu, China.ORCID 0000-0003-2778-6165
Cheng Zhang *Institute of Aging & Tissue Regeneration, Ren-Ji Hospital, Shanghai Jiao Tong University School of Medicine (SJTU-SM), 200127, Shanghai, China.
Xinci ShangJiangsu Key Laboratory of Neuropsychiatric Diseases, Jiangsu Province Engineering Research Center of Precision Diagnostics and Therapeutics Development, College of Pharmaceutical Sciences, Soochow University, 215123, Suzhou, Jiangsu, China.
Yichang ChenJiangsu Key Laboratory of Neuropsychiatric Diseases, Jiangsu Province Engineering Research Center of Precision Diagnostics and Therapeutics Development, College of Pharmaceutical Sciences, Soochow University, 215123, Suzhou, Jiangsu, China.
Qin XiaoJiangsu Key Laboratory of Neuropsychiatric Diseases, Jiangsu Province Engineering Research Center of Precision Diagnostics and Therapeutics Development, College of Pharmaceutical Sciences, Soochow University, 215123, Suzhou, Jiangsu, China.
Zhengguo WeiSchool of Biology and Basic Medical Science, Soochow University, 215123, Suzhou, Jiangsu, China.
Guanghui WangJiangsu Key Laboratory of Neuropsychiatric Diseases, Jiangsu Province Engineering Research Center of Precision Diagnostics and Therapeutics Development, College of Pharmaceutical Sciences, Soochow University, 215123, Suzhou, Jiangsu, China.ORCID 0000-0001-8551-6468
Xuechu ZhenJiangsu Key Laboratory of Neuropsychiatric Diseases, Jiangsu Province Engineering Research Center of Precision Diagnostics and Therapeutics Development, College of Pharmaceutical Sciences, Soochow University, 215123, Suzhou, Jiangsu, China.
Guoqiang XuJiangsu Key Laboratory of Neuropsychiatric Diseases, Jiangsu Province Engineering Research Center of Precision Diagnostics and Therapeutics Development, College of Pharmaceutical Sciences, Soochow University, 215123, Suzhou, Jiangsu, China.ORCID 0000-0002-4753-4769
Jinrong MinHubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, 430079, Wuhan, Hubei, China.ORCID 0000-0001-5210-3130
Shaoming ShenInstitute of Aging & Tissue Regeneration, Ren-Ji Hospital, Shanghai Jiao Tong University School of Medicine (SJTU-SM), 200127, Shanghai, China. smshen@shsmu.edu.cn.ORCID 0000-0001-8334-9790
Yanli LiuJiangsu Key Laboratory of Neuropsychiatric Diseases, Jiangsu Province Engineering Research Center of Precision Diagnostics and Therapeutics Development, College of Pharmaceutical Sciences, Soochow University, 215123, Suzhou, Jiangsu, China. ylliu18@suda.edu.cn.ORCID 0000-0003-0197-7617

Funding

National Natural Science Foundation of China (National Science Foundation of China) 32271309
6 · The paper itself

Abstract

PTENα/β, two variants of PTEN, play a key role in promoting tumor growth by interacting with WDR5 through their N-terminal extensions (NTEs). This interaction facilitates the recruitment of the SET1/MLL methyltransferase complex, resulting in histone H3K4 trimethylation and upregulation of oncogenes such as NOTCH3, which in turn promotes tumor growth. However, the molecular mechanism underlying this interaction has remained elusive. In this study, we determined the first crystal structure of PTENα-NTE in complex with WDR5, which reveals that PTENα utilizes a unique binding motif of a sequence SSSRRSS found in the NTE domain of PTENα/β to specifically bind to the WIN site of WDR5. Disruption of this interaction significantly impedes cell proliferation and tumor growth, highlighting the potential of the WIN site inhibitors of WDR5 as a way of therapeutic intervention of the PTENα/β associated cancers. These findings not only shed light on the important role of the PTENα/β-WDR5 interaction in carcinogenesis, but also present a promising avenue for developing cancer treatments that target this pathway.

Indexed as

Intracellular Signaling Peptides and ProteinsPTEN PhosphohydrolaseAmino Acid MotifsAnimalsCell Line, TumorCell ProliferationDisease ProgressionHistone-Lysine N-MethyltransferaseHumansMiceMice, NudeNeoplasmsProtein BindingProtein DomainsHistone-Lysine N-MethyltransferaseIntracellular Signaling Peptides and ProteinsPTEN PhosphohydrolasePTEN protein, humanWDR5 protein, human

Identifiers

PMID38744853
PMCPMC11094138

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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.