Mechanisms of nuclear localization of the progesterone receptor.
Deletion mutants of the rabbit progesterone receptor were used to identify two major mechanisms of its nuclear localization. A putative signal sequence, homologous to that of the SV40 large T antigen, was localized around amino acids 638-642 and was shown to be constitutively active. When amino acids 638-642 were deleted, the receptor became cytoplasmic but could be shifted into the nucleus by the addition of hormone (or anti-hormone), it was almost fully active. A second putative nuclear localization signal is located in the DNA binding domain activated either through ligand binding or through production of constitutive receptor. By deleting epitopes recognized by monoclonal antibodies, it was possible to follow different receptor mutants inside the same cells. In the absence of ligand the receptor was transferred into the nucleus as a monomer. After administration of hormone (or anti-hormone) a "cytoplasmic" monomer was transferred into the nucleus through interaction with a "nuclear" monomer. These interactions occurred through the steroid binding domains of both monomers.
Guiochon-Mantel
A
A
Hormones et Reproduction (INSERM U. 135), Faculté de Médecine Paris-Sud, Le Kremlin-Bicêtre, France.
Loosfelt
H
H
Lescop
P
P
Christin-Maitre
S
S
Perrot-Applanat
M
M
Milgrom
E
E
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D002872:Chromosome Deletion; D003593:Cytoplasm / Q000378:metabolism; D004247:DNA / Q000235:genetics; D046911:Macromolecular Substances; D015735:Mifepristone / Q000494:pharmacology; D011499:Protein Processing, Post-Translational; D021382:Protein Sorting Signals / Q000235:genetics* / Q000378:metabolism; D011817:Rabbits; D011980:Receptors, Progesterone / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
D000952:Antigens, Polyomavirus Transforming; D046911:Macromolecular Substances; D021382:Protein Sorting Signals; D011980:Receptors, Progesterone; D015735:Mifepristone; D004247:DNA; D015500:Chloramphenicol O-Acetyltransferase