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HUWE1 is involved in Sertoli cell polarity establishment by ubiquitination mediated degradation of WT1

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资源类型：
Pubmed体系：
作者：
Liu Bowen[1,2,3] * ; Wang Mengyue[4,5] * ; Cen Changhuo[6] * ; Shen Zhiming[1,2] ; Li Jiayi[1,2,3] ; Cui Xiuhong[1,2,3] ; Zhao Xudong[7] ; Chen Min[1,2,3,8] ; Gao Fei[1,2,3,8] ;
机构： [1]State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. [2]Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China. [3]University of Chinese Academy of Sciences, Beijing, China. [4]State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan, Shandong, China. [5]National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong, China. [6]State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Inner Mongolia Key Laboratory for Molecular Regulation of the Cell, School of Life Sciences, Inner Mongolia University, Hohhot, Inner Mongolia, China. [7]Department of Targeting Therapy & Immunology and Laboratory of Cell Engineering & Immunotherapy, Cancer Center, State Key Laboratory of Respiratory Health and Multimorbidity and Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China [8]Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China
出处：
DOI： 10.1007/s00018-025-05779-6
ISSN：

关键词： Huwe1 Wt1 Sertoli cell polarity Ubiquitination

摘要：
HUWE1, a member of HECT E3 ubiquitin ligase family, is implicated in a variety of cellular processes. Recent studies find that HUWE1 also plays critical roles in germ cell development and inactivation of HUWE1 causes germ cell loss in both male and female mice. In this study, we found that Huwe1 was also highly expressed in testicular Sertoli cells. Inactivation of Huwe1 in Sertoli cells resulted in loss of cell polarity, which in turn caused germ cells loss and male infertility. Further study revealed that dysregulation in the expression of cytoskeletal and adhesion-related molecules, as well as a significant increase in EMT-related trans-factors SNAI1&2 in Huwe1-deficient Sertoli cells. Intriguingly, the protein level of WT1 was significantly increased in Huwe1-deficient Sertoli cells, and overexpression of Wt1 in Sertoli cells also caused the defects in spermatogenesis which was consistent with Huwe1 CKO mouse model. Furthermore, the defect of spermatogenesis in Huwe1 CKO mice was partially rescued by deleting one allele of Wt1 gene. Mechanistic studies revealed that WT1 interacts with HUWE1 protein and it could be ubiquitinated by HUWE1. Our study demonstrates that HUWE1 is involved in the establishment of Sertoli cell polarity mainly by regulating the protein level of WT1 gene.© 2025. The Author(s).

基金：
This work was supported by: (1) the National Key R&D Pro­gram of China (2022YFC2702400); (2) the National Natural Science Foundation of China (32270902 and 32170855); (3) the Faculty Re­sources Project of the College of Life Sciences, Inner Mongolia Uni­versity (2022 − 104); (4) the Initiative Scientific Research Program, Institute of Zoology, Chinese Academy of Sciences (2023IOZ0102).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2025]版：
大类 | 2 区 生物学
小类 | 2 区 生化与分子生物学 2 区 细胞生物学
最新[2025]版：
大类 | 2 区 生物学
小类 | 2 区 生化与分子生物学 2 区 细胞生物学
第一作者：
第一作者机构： [1]State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. [2]Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China. [3]University of Chinese Academy of Sciences, Beijing, China.
共同第一作者：
通讯作者：
通讯机构： [1]State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. [2]Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China. [3]University of Chinese Academy of Sciences, Beijing, China. [8]Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China
推荐引用方式(GB/T 7714)：
Liu Bowen,Wang Mengyue,Cen Changhuo,et al.HUWE1 is involved in Sertoli cell polarity establishment by ubiquitination mediated degradation of WT1[J].Cellular And Molecular Life Sciences : CMLS.2025,82(1):271.doi:10.1007/s00018-025-05779-6.
APA：
Liu Bowen,Wang Mengyue,Cen Changhuo,Shen Zhiming,Li Jiayi...&Gao Fei.(2025).HUWE1 is involved in Sertoli cell polarity establishment by ubiquitination mediated degradation of WT1.Cellular And Molecular Life Sciences : CMLS,82,(1)
MLA：
Liu Bowen,et al."HUWE1 is involved in Sertoli cell polarity establishment by ubiquitination mediated degradation of WT1".Cellular And Molecular Life Sciences : CMLS 82..1(2025):271

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