Mechanisms of nuclear localization of the progesterone receptor: evidence for interaction between monomers.
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 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. The second mechanism consisted of the activation of the DNA binding domain. 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, Le Kremlin-Bicêtre, France.
Loosfelt
H
H
Lescop
P
P
Sar
S
S
Atger
M
M
Perrot-Applanat
M
M
Milgrom
E
E
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002451:Cell Compartmentation; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000502:physiology; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000276:immunology / Q000378:metabolism*; D004963:Estrenes / Q000494:pharmacology; D015735:Mifepristone; D009687:Nuclear Proteins / Q000378:metabolism*; D011374:Progesterone / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011817:Rabbits; D011980:Receptors, Progesterone / Q000276:immunology / Q000378:metabolism*; D014162:Transfection
D000911:Antibodies, Monoclonal; D004268:DNA-Binding Proteins; D004963:Estrenes; D009687:Nuclear Proteins; D011980:Receptors, Progesterone; D015735:Mifepristone; D011374:Progesterone