GSK-3beta mediates in the progesterone inhibition of estrogen induced cyclin D2 nuclear localization and cell proliferation in cyclin D1-/- mouse uterine epithelium.
We report that glycogen synthase kinase (GSK)-3beta is phosphorylated at ser9 and inactivated in uterine epithelial cells from E(2)-treated cyclin D1 null mutant mice. Simultaneous administration of P(4) together with E(2) blocked this effect. Pharmacological inhibition of GSK-3beta activity in mice treated with P(4)E(2) reversed the nuclear exclusion of cyclin D2 in the uterine epithelial cells and this caused phosphorylation of Rb protein and progression of cells towards S-phase. Our results indicate that GSK-3beta is a major target of E(2) and P(4) in regulation of cyclin D2 localization in the mouse uterine epithelium.
Wang
Yuxiang
Y
School of Life Science and National Key Laboratory of Genetic Engineering, Fudan University, Shanghai 200433, PR China.
Feng
Hui
H
Bi
Cheng
C
Zhu
Liyin
L
Pollard
Jeffrey W
JW
Chen
Bo
B
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects*; D056742:Cyclin D2; D016213:Cyclins / Q000378:metabolism*; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D019940:Genes, bcl-1; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism / Q000502:physiology*; D000071679:Glycogen Synthase Kinase 3 beta; D066298:In Vitro Techniques; D051379:Mice; D018345:Mice, Knockout; D010766:Phosphorylation / Q000187:drug effects; D011374:Progesterone / Q000494:pharmacology*; D016160:Retinoblastoma Protein / Q000378:metabolism; D014599:Uterus / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism
C486196:Ccnd2 protein, mouse; D056742:Cyclin D2; D016213:Cyclins; D016160:Retinoblastoma Protein; D011374:Progesterone; D004958:Estradiol; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3