Evidence map›Paper›PMID 41530531›Full record

ArticleNature chemical biology2026

Autopalmitoylation of IDH1-R132H regulates its neomorphic activity in cancer cells.

Lu Hu, Jinyu Lin, Liping Sun, Alison M Berezuk, Katharine S Tuttle, Xing Zhu, Hyuk-Soo Seo, Sirano Dhe-Paganon, Pan Li, Yang Sun and 11 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature chemical biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

21 authors.

Lu HuCutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA. lhu8@mgh.harvard.edu.ORCID http://orcid.org/0000-0002-1594-8828
Jinyu LiniHuman Institute, Shanghai Tech University, Shanghai, China.
Liping SuniHuman Institute, Shanghai Tech University, Shanghai, China.ORCID http://orcid.org/0000-0002-2420-8936
Alison M BerezukDepartment of Biochemistry & Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada.
Katharine S TuttleDepartment of Biochemistry & Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada.
Xing ZhuDepartment of Biochemistry & Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada.
Hyuk-Soo SeoDepartment of Biological Chemistry & Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0003-0646-2102
Sirano Dhe-PaganonDepartment of Biological Chemistry & Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0003-0824-5929
Pan LiCancer Institute, Xuzhou Medical University, Xuzhou, China.
Yang SunCutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
Lisheng NiDepartment of Biophysics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Jianan ZhangCutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
Dazhi TanAntidote Health Foundation for Cure of Cancer, Cambridge, MA, USA.
Hiroaki WakimotoDepartment of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-8225-241X
Daniel P CahillDepartment of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Xiaochen BaiDepartment of Biophysics, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID http://orcid.org/0000-0002-4234-5686
Xuelian LuoDepartment of Biophysics, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID http://orcid.org/0000-0002-5058-4695
John M AsaraMass Spectrometry Core, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-7450-2589
Sriram SubramaniamDepartment of Biochemistry & Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada.
Yibing ShaniHuman Institute, Shanghai Tech University, Shanghai, China. shanyb@shanghaitech.edu.cn.ORCID http://orcid.org/0000-0002-3865-8110
Xu WuCutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA. xuwu@mgh.harvard.edu.ORCID http://orcid.org/0000-0002-1624-0143

Funding

Massachusetts General Hospital (MGH) ECOR psotdoc fellowshipMassachusetts General Hospital (MGH) ISF
6 · The paper itself

Abstract

Gain-of-function mutations of isocitrate dehydrogenase 1 (IDH1) lead to oncometabolite (R)-2-hydroxyglutarate production, contributing to the tumorigenesis of multiple human cancers. While fatty acid biosynthesis is critical for IDH1-mutant tumor growth, the underlying mechanisms remain unclear. Here, leveraging chemical probes and chemoproteomic profiling, we identified that oncogenic IDH1-R132H is uniquely autopalmitoylated at C269, which is not observed in wild-type IDH1. This modification responds to fatty acids and regulates R132H enzymatic activity by enhancing substrate and cofactor binding, as well as dimerization. Loss of C269 palmitoylation reverses IDH1-R132H-induced metabolic reprogramming and hypermethylation phenotypes and impairs cell transformation. Interestingly, C269 autopalmitoylation occurs within a hydrophobic pocket, targeted by a clinical IDH1-mutant inhibitor (LY3410738). Our study reveals that autopalmitoylation, conferred by the IDH1

Indexed as

Isocitrate DehydrogenaseLipoylationNeoplasmsAnimalsCell Line, TumorFatty AcidsGlutaratesHumansMutationalpha-hydroxyglutarateFatty AcidsGlutaratesIDH1 protein, humanIsocitrate Dehydrogenase

Identifiers

PMID41530531

What OpenQuestion holds

Textmetadata
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.