Cyclosporin A promotes nuclear transfer of a cytoplasmic progesterone receptor mutant.
The effects of cyclosporin A (CsA), FK506 and rapamycin (Rapa) on the intracellular localization of a mutated rabbit progesterone receptor (PR) which lacks the main constitutive nuclear localization signal (NLS) (delta 638-642) and is cytoplasmic in the absence of progesterone (Prog), were assayed by indirect immunofluorescence in Lcl3 cells, a mouse L-cell line stably expressing this mutant. CsA alone, at 5-10 microM concentrations, induced almost complete nuclear transfer of the PR-mutant within 18 h. In contrast, FK506 and Rapa at the same concentrations had no effect. This nuclear transfer induced by CsA was concentration and time dependent and was independent of protein synthesis. It was not a potentiation of hormone action since it took place in the absence of hormone, including in serum-free culture conditions. The implications of this specific effect of CsA are discussed.
Jung-Testas
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I
INSERM U. 33, Le Kremlin-Bicêtre, France.
Lebeau
M C
MC
Catelli
M G
MG
Baulieu
E E
EE
D000818:Animals; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology*; D003593:Cytoplasm / Q000737:chemistry; D005347:Fibroblasts / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000494:pharmacology; D051379:Mice; D015735:Mifepristone / Q000494:pharmacology; D009154:Mutation; D011090:Polyenes / Q000494:pharmacology; D011817:Rabbits; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism*; D020123:Sirolimus; D016559:Tacrolimus / Q000494:pharmacology; D013997:Time Factors
D007166:Immunosuppressive Agents; D011090:Polyenes; D011980:Receptors, Progesterone; D015735:Mifepristone; D016572:Cyclosporine; D020123:Sirolimus; D016559:Tacrolimus