ArticleProceedings of the National Academy of Sciences of the United States of America2022
P38α MAPK is a gatekeeper of uterine progesterone responsiveness at peri-implantation via Ube3c-mediated PGR degradation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 21 citations in OpenAlex.
- SAV1 in Cooperation With FKBP52 Participates in Implantation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The Role of Immunologic Factors in Endometrial Receptivity: An Embryo-Endometrium Dialogue.International journal of molecular sciences · 2026Review
- CRL4International journal of biological sciences · 2026Article
- Endometrial aging is accompanied by H3K27ac and PGR loss.Nature aging · 2025Article
- Targeting TTK Inhibits Tumorigenesis of T-Cell Lymphoma Through Dephosphorylating p38α and Activating AMPK/mTOR Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Comprehensive analysis based on the ubiquitination- and deubiquitylation-related genes reveals the function of NEURL3 in esophageal squamous cell carcinoma.Frontiers in immunology · 2025Article
- Varied cellular abnormalities in thin vs. normal endometrium in recurrent implantation failure by single-cell transcriptomics.Reproductive biology and endocrinology : RB&E · 2024Article
- Phosphorylation of IDH1 Facilitates Progestin Resistance in Endometrial Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Stromal Pbrm1 mediates chromatin remodeling necessary for embryo implantation in the mouse uterus.The Journal of clinical investigation · 2024Article
- Article
- Basic Research Advances in China on Embryo Implantation, Placentation, and Parturition.Maternal-fetal medicine (Wolters Kluwer Health, Inc.) · 2024Article
- METTL3 is essential for normal progesterone signaling during embryo implantation via mProceedings of the National Academy of Sciences of the United States of America · 2023Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Estrogen and progesterone specify the establishment of uterine receptivity mainly through their respective nuclear receptors, ER and PR. PR is transcriptionally induced by estrogen-ER signaling in the endometrium, but how the protein homeostasis of PR in the endometrium is regulated remains elusive. Here, we demonstrated that the uterine-selective depletion of P38α derails normal uterine receptivity ascribed to the dramatic down-regulation of PR protein and disordered progesterone responsiveness in the uterine stromal compartment, leading to defective implantation and female infertility. Specifically, Ube3c, an HECT family E3 ubiquitin ligase, targets PR for polyubiquitination and thus proteasome degradation in the absence of P38α. Moreover, we discovered that P38α restrains the polyubiquitination activity of Ube3c toward PR by phosphorylating the Ube3c at serine741 . In summary, we provided genetic evidence for the regulation of PR protein stability in the endometrium by P38α and identified Ube3c, whose activity was modulated by P38α-mediated phosphorylation, as an E3 ubiquitin ligase for PR in the uterus.
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