Acetylation-triggered degradation of MSX1 impairs palatal development.

Li Meng, Jiawen You, Zhongyin Zhang, Yucheng Jiang, Yulan Liu, Mingliang Zhou, Junqing Ma, Xinquan Jiang

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

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8 authors.

Li Meng *Department of Prosthodontics, Shanghai Ninth People' s Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Engineering Research Center of Advanced Dental Technology and Materials, Shanghai, China.ORCID http://orcid.org/0009-0007-6413-308X

Jiawen You *Stomatological Hospital affiliated Suzhou Vocational Health College, Suzhou, China.

Zhongyin ZhangState Key Laboratory Cultivation Base of Research, Prevention and Treatment for Oral Diseases, Nanjing Medical University, Nanjing, China.

Yucheng JiangState Key Laboratory Cultivation Base of Research, Prevention and Treatment for Oral Diseases, Nanjing Medical University, Nanjing, China.

Yulan LiuDepartment of Prosthodontics, Shanghai Ninth People' s Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Engineering Research Center of Advanced Dental Technology and Materials, Shanghai, China.

Mingliang ZhouShanghai Stomatological Hospital, Fudan University, Shanghai, China. mingliangzhou@aliyun.com.ORCID http://orcid.org/0000-0003-4375-3312

Junqing MaSavaid Stomatology School, Hangzhou Medical College, Hangzhou, China. majunq@163.com.ORCID http://orcid.org/0000-0002-3074-8912

Xinquan JiangDepartment of Prosthodontics, Shanghai Ninth People' s Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Engineering Research Center of Advanced Dental Technology and Materials, Shanghai, China. xinquanjiang@aliyun.com.ORCID http://orcid.org/0000-0002-1490-281X

Funding

China Postdoctoral Science Foundation BX20250199National Natural Science Foundation of China (National Science Foundation of China) 82130027

6 · The paper itself

Abstract

Cleft palate, a prevalent congenital disorder, arises from dysregulated embryonic palatal fusion, but the posttranslational modifications (PTMs) driving this process remain poorly understood. Here, we report that lysine acetylation is a critical MSX1 proteostasis switch that governs embryonic palatal mesenchymal (EPM) cell survival. We demonstrate in vitro and in vivo that MSX1 protein stability regulation by deacetylase SIRT1-catalyzed acetylation underlies EPM apoptosis and palatal fusion. In atRA-induced cleft palate models, SIRT1 suppression drives MSX1 hyperacetylation, accelerating proteasomal degradation and culminating in EPM apoptosis. Strikingly, transcriptomic profiling revealed the exclusive proteostatic role of acetylation, indicating that MSX1's structural stability differs from its transcriptional activity-a paradigm distinct from that of classic PTM mechanisms during development. Lentivirus-mediated delivery of the deacetylase SIRT1 or the deacetylation mimic MSX1 K139R significantly reduced cleft severity, indicating its preventive and therapeutic potential in humans. Our work establishes the MSX1 acetylation as both a pathogenic driver and a druggable target in cleft palate, redefining PTM regulation as a central etiological factor in genetic disorders.

Identifiers

PMID41856994

DOI10.1038/s41420-026-03018-w

PMCPMC13039415

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LicenceCC BY

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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 Socratic graph.