The intranuclear prolactin/cyclophilin B complex as a transcriptional inducer.

Abstract

The nuclear translocation of peptide hormones, such as the somatolactogenic hormone prolactin, after receptor internalization has been widely reported. Prolactin has been demonstrated to interact with cyclophilin B, a member of the immunophilin family of proteins. Cyclophilin B interaction with prolactin potentiated prolactin-induced proliferation, cell growth, and the nuclear retrotransport of prolactin. These effects could be abrogated by the removal of the peptidyl-prolyl isomerase activity of cyclophilin B. Our findings indicate that the intranuclear prolactin/cyclophilin B complex acts as a transcriptional inducer by interacting directly with Stat5, resulting in the removal of the Stat-repressor protein inhibitor of activated Stat 3 (PIAS3), thereby enhancing Stat5 DNA-binding activity and prolactin-induced, Stat5-mediated gene expression.