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HUWE1 is involved in Sertoli cell polarity establishment by ubiquitination mediated degradation of WT1
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HUWE1 is involved in Sertoli cell polarity establishment by ubiquitination mediated degradation of WT1
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Journal Article
HUWE1 is involved in Sertoli cell polarity establishment by ubiquitination mediated degradation of WT1
2025
Overview
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.
Publisher
Springer International Publishing,Springer Nature B.V,Springer
Subject
/ Animals
/ Biomedical and Life Sciences
/ Defects
/ family
/ females
/ Huwe1
/ Infertility, Male - genetics
/ Infertility, Male - metabolism
/ Infertility, Male - pathology
/ Male
/ Males
/ Mice
/ Polarity
/ Proteins
/ Sperm
/ Testes
/ Ubiquitin-Protein Ligases - genetics
/ Ubiquitin-Protein Ligases - metabolism
/ Wt1
