Evidence map›Paper›PMID 41688443›Full record

ArticleCell death & disease2026

USP30-mediated Deubiquitination of Hexokinase 2 controls the metabolic fate of glucose and tumor progression.

Zhang Haowei, Xiaolin Li, Weijie Liao, Xuan Qin, Yapei Jiang, Haitao Yang, Hongli Zeng, Yuetong Li, Weidong Xie, Yaou Zhang and 1 more

Erratum issuedAbstract read
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In one paragraph

Article in Cell death & disease, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Zhang Haowei *School of Food and Drug, Shenzhen Polytechnic University, Shenzhen, China.
Xiaolin Li *State Key Laboratory of Chemical Oncogenomics, Institute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, China.
Weijie Liao *Department of Hematology and Oncology, International Cancer Center, Shenzhen University General Hospital, Shenzhen University, Shenzhen, China.ORCID http://orcid.org/0000-0001-6507-2919
Xuan QinFuwai Shenzhen Hospital, Chinese Academy of Medical Sciences, Shenzhen, China.
Yapei JiangState Key Laboratory of Chemical Oncogenomics, Institute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, China.
Haitao YangState Key Laboratory of Chemical Oncogenomics, Institute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, China.
Hongli ZengState Key Laboratory of Chemical Oncogenomics, Institute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, China.
Yuetong LiState Key Laboratory of Chemical Oncogenomics, Institute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, China.
Weidong XieState Key Laboratory of Chemical Oncogenomics, Institute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, China.
Yaou ZhangState Key Laboratory of Chemical Oncogenomics, Institute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen, China.ORCID http://orcid.org/0000-0002-2501-8093
Naihan XuSchool of Food and Drug, Shenzhen Polytechnic University, Shenzhen, China. xu_naihan@szpu.edu.cn.ORCID http://orcid.org/0000-0001-5457-6863

Funding

National Natural Science Foundation of China (National Science Foundation of China) 32200438, 32301053Science and Technology Department of Henan Province (Henan Provincial Department of Science and Technology) 252102310403Shenzhen Science and Technology Innovation Commission JCYJ20240813142003005
6 · The paper itself

Abstract

The mitochondria-localized deubiquitinase USP30 regulates mitophagy and mitochondrial homeostasis, playing a significant role in the progression of neurodegenerative diseases. However, its role in cancer remains poorly understood. Through metabolism-related gene set enrichment analysis, we identified USP30 as a key modulator of glucose metabolism in cancer cells. Utilizing quantitative proteomic and ubiquitinomic approaches coupled with co-immunoprecipitation assays, we elucidated that USP30 regulates glycolysis by interacting with hexokinase HK1 and HK2, a process dependent on its enzymatic activity. USP30 modulates the ubiquitination profile of HK1 and HK2 by preferentially removing atypical ubiquitin chains, thereby enhancing their stability, mitochondrial localization, VDAC1 binding and hexokinase activity. Lysine 144 emerges as a critical regulatory site for USP30-mediated deubiquitination of HK2. Mutation of K144 enhances HK2 stability, increases its mitochondrial localization and binding to VDAC1, and significantly augments hexokinase activity. Furthermore, the HK2 K144 mutation markedly enhances tumor cell glycolysis, fostering increased proliferation and migration both in vitro and in vivo. These findings underscore USP30 as a novel regulator of glycolysis in cancer cells via modulation of HK2 ubiquitination dynamics, suggesting its potential as a therapeutic target in cancer metabolism.

Indexed as

GlucoseHexokinaseNeoplasmsThiolester HydrolasesAnimalsCell Line, TumorCell ProliferationDisease ProgressionGlycolysisHumansMiceMice, NudeMitochondriaMitochondrial ProteinsUbiquitinationUbiquitin ThiolesteraseGlucoseHexokinaseHK1 protein, humanHK2 protein, humanMitochondrial ProteinsThiolester HydrolasesUbiquitin ThiolesteraseUsp30 protein, humanVDAC1 protein, humanVoltage-Dependent Anion Channel 1

Identifiers

PMID41688443
PMCPMC12921045

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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.