Evidence map›Paper›PMID 39032648›Full record

ArticleThe Journal of biological chemistry2024

The ubiquitin ligase UBR4 and the deubiquitylase USP5 modulate the stability of DNA mismatch repair protein MLH1.

Chenyu Mao, Siqi Li, Jun Che, Dongzhou Liu, Xinliang Mao, Hai Rao

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PubMed Full text at PMC Publisher
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Article in The Journal of biological chemistry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

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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

4 citing papers in PubMed.

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4 · The record

Corrections and comments

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5 · Who and what money

Authors and funding

6 authors.

Chenyu MaoDepartment of Biochemistry, School of Medicine, Southern University of Science and Technology, Shenzhen, China.
Siqi LiDepartment of Biochemistry, School of Medicine, Southern University of Science and Technology, Shenzhen, China.
Jun CheDepartment of Biochemistry, School of Medicine, Southern University of Science and Technology, Shenzhen, China.
Dongzhou LiuDepartment of Rheumatology and Immunology, Shenzhen People's Hospital, Shenzhen, Guangdong, China; The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, Guangdong, China.
Xinliang MaoGuangdong Provincial Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong, China. Electronic address: xinliangmao@gzhmu.edu.cn.
Hai RaoDepartment of Biochemistry, School of Medicine, Southern University of Science and Technology, Shenzhen, China; Key University Laboratory of Metabolism and Health of Guangdong, Southern University of Science and Technology, Shenzhen, China. Electronic address: raoh@sustech.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

MLH1 plays a critical role in DNA mismatch repair and genome maintenance. MLH1 deficiency promotes cancer development and progression, but the mechanism underlying MLH1 regulation remains enigmatic. In this study, we demonstrated that MLH1 protein is degraded by the ubiquitin-proteasome system and have identified vital cis-elements and trans-factors involved in MLH1 turnover. We found that the region encompassing the amino acids 516 to 650 is crucial for MLH1 degradation. The mismatch repair protein PMS2 may shield MLH1 from degradation as it binds to the MLH1 segment key to its turnover. Furthermore, we have identified the E3 ubiquitin ligase UBR4 and the deubiquitylase USP5, which oppositely modulate MLH1 stability. In consistence, UBR4 or USP5 deficiency affects the cellular response to nucleotide analog 6-TG, supporting their roles in regulating mismatch repair. Our study has revealed important insights into the regulatory mechanisms underlying MLH1 proteolysis, critical to DNA mismatch repair related diseases.

Indexed as

DNA Mismatch RepairMutL Protein Homolog 1ProteolysisUbiquitin-Protein LigasesHEK293 CellsHumansMismatch Repair Endonuclease PMS2Protein StabilityUbiquitin-Specific ProteasesMismatch Repair Endonuclease PMS2MLH1 protein, humanMutL Protein Homolog 1PMS2 protein, humanUbiquitin-Protein LigasesUbiquitin-Specific ProteasesdeubiquitylaseDNA mismatch repairE3 ligaseMLH1ubiquitin

Identifiers

PMID39032648
PMCPMC11375253

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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.