{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T02:21:28Z","timestamp":1792203688338,"version":"4.4.0"},"reference-count":45,"publisher":"National Academy of Sciences","issue":"32","license":[{"start":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T00:00:00Z","timestamp":1659312000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2022,8,9]]},"abstract":"<jats:p>Estrogen and progesterone specify the establishment of uterine receptivity mainly through their respective nuclear receptors, ER and PR. PR is transcriptionally induced by estrogen\u2013ER 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 P38\u03b1 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 P38\u03b1. Moreover, we discovered that P38\u03b1 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 P38\u03b1 and identified Ube3c, whose activity was modulated by P38\u03b1-mediated phosphorylation, as an E3 ubiquitin ligase for PR in the uterus.<\/jats:p>","DOI":"10.1073\/pnas.2206000119","type":"journal-article","created":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T15:22:29Z","timestamp":1659367349000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":26,"title":["P38\u03b1 MAPK is a gatekeeper of uterine progesterone responsiveness at peri-implantation via Ube3c-mediated PGR degradation"],"prefix":"10.1073","volume":"119","author":[{"given":"Yedong","family":"Tang","sequence":"first","affiliation":[{"name":"Fujian Provincial Key Laboratory for Developmental Biology and Neurosciences, College of Life Sciences, Fujian Normal University, Fuzhou, Fujian, 350007, China"},{"name":"Fujian Provincial Key Laboratory of 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