Evidence map›Paper›PMID 41951593›Full record

ArticleNature communications2026

NLRP14 modulates the activity of E3 ubiquitin ligases during the oocyte-to-embryo transition.

Sibei Liu, Qianqian Qi, Pengliang Chi, Haizhan Jiao, Li Yan, Yuechao Lu, Rongrong Zhang, Jinhong Li, Sicheng Ju, Zhuo Han and 12 more

Abstract read
In one paragraph

Article in Nature communications, 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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0citing papers in PubMed
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1 · What the graph read from it

What it found

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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

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

22 authors.

Sibei Liu *Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University, Chengdu, China.ORCID http://orcid.org/0000-0001-6996-8245
Qianqian Qi *Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University, Chengdu, China.
Pengliang Chi *Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University, Chengdu, China.ORCID http://orcid.org/0000-0002-6942-603X
Haizhan Jiao *Department of Biomedical Sciences, Kobilka Institute of Innovative Drug Discovery, Division of Biomedical Health Sciences, School of Medicine, The Chinese University of Hong Kong, ShenZhen, Shenzhen, China.
Li Yan *Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University, Chengdu, China.
Yuechao LuDepartment of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University, Chengdu, China.ORCID http://orcid.org/0000-0002-7332-7819
Rongrong ZhangCenter for Reproductive Medicine, Shandong University, Jinan, China.
Jinhong LiDepartment of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University, Chengdu, China.ORCID http://orcid.org/0000-0003-2448-1067
Sicheng JuDepartment of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University, Chengdu, China.ORCID http://orcid.org/0009-0003-3503-4876
Zhuo HanDepartment of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University, Chengdu, China.ORCID http://orcid.org/0000-0003-0466-4122
Zihan ZhangDepartment of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University, Chengdu, China.
Qingting LiuDepartment of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University, Chengdu, China.
Guojin OuDepartment of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University, Chengdu, China.ORCID http://orcid.org/0000-0003-4599-7951
Jialu LiDepartment of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University, Chengdu, China.ORCID http://orcid.org/0000-0002-0513-7597
Jing ChenLaboratory of Pediatric Surgery, Department of Pediatric Surgery, West China Hospital, Sichuan University, Chengdu, China.ORCID http://orcid.org/0000-0001-5540-0878
Xiang WangDepartment of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University, Chengdu, China.ORCID http://orcid.org/0000-0001-9348-7441
Lei LiThe Key Laboratory of Organ Regeneration and Reconstruction, Beijing Institute of Stem Cell and Regenerative Medicine, Institute of Zoology; University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, China.ORCID http://orcid.org/0000-0001-5478-5681
Li GuoDepartment of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University, Chengdu, China.
Xue JiaoCenter for Reproductive Medicine, Shandong University, Jinan, China. jiaoxue@sdu.edu.cn.ORCID http://orcid.org/0000-0002-2936-2166
Hongli HuDepartment of Biomedical Sciences, Kobilka Institute of Innovative Drug Discovery, Division of Biomedical Health Sciences, School of Medicine, The Chinese University of Hong Kong, ShenZhen, Shenzhen, China. honglihu@cuhk.edu.cn.ORCID http://orcid.org/0000-0003-3658-272X
Yongmei JiangDepartment of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University, Chengdu, China. jiangym_SCU@163.com.
Dong DengDepartment of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University, Chengdu, China. dengd@scu.edu.cn.ORCID http://orcid.org/0000-0002-8590-9525

Funding

National Science Foundation of China | National Natural Science Foundation of China-Yunnan Joint Fund (NSFC-Yunnan Joint Fund) 82401959
6 · The paper itself

Abstract

NLRP14 is an essential maternal factor for mammalian embryonic development. Maternal ablation of NLRP14 in mice impairs DNA demethylation and calcium homeostasis in zygotes, causing early embryonic arrest. However, the underlying biochemical events remain largely unknown. Here, we identified two binding partners (KDM2A and UHRF1) of NLRP14 and further solved structures of NLRP14-KDM2A-SKP1 and NLRP14-UHRF1. Structural analysis revealed that NLRP14 modulates the SKP1-CUL1-F-box (SCF) E3 ubiquitin ligase and the RING-type E3 ubiquitin ligase UHRF1 through two distinct mechanisms. Mechanistically, NLRP14 competitively inhibits KDM2A-mediated SCF assembly or allosterically inhibits the activity of UHRF1 by occupying the E2 ubiquitin-conjugating enzyme (UBE2D) binding site of the ubiquitin-like (UBL) domain. Deletion of NLRP14 in mice increases ubiquitination levels in oocytes during maturation and after fertilization. Collectively, our findings identify NLRP14 as a dual regulator that restrains E3 ubiquitin ligase-driven ubiquitination by limiting SCF complex assembly and attenuating UHRF1 activity. This regulatory role is required to prevent excessive protein ubiquitination and maintain proteostasis during the oocyte-to-embryo transition, thereby supporting early embryonic development. Our study uncovers maternal regulation of proteostasis in oocytes and suggests that dysregulating proteostasis is an important factor in the pathogenesis of reproductive disorders.

Indexed as

Intracellular Signaling Peptides and ProteinsOocytesUbiquitin-Protein LigasesAnimalsCCAAT-Enhancer-Binding ProteinsEmbryonic DevelopmentF-Box ProteinsFemaleHumansMiceMice, KnockoutProtein BindingSKP Cullin F-Box Protein LigasesUbiquitinationCCAAT-Enhancer-Binding ProteinsF-Box ProteinsIntracellular Signaling Peptides and ProteinsSKP Cullin F-Box Protein LigasesUbiquitin-Protein LigasesUhrf1 protein, mouse

Identifiers

PMID41951593
PMCPMC13237083

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