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The intranuclear prolactin/cyclophilin B complex as a transcriptional inducer
Michael A Rycyzyn1, Charles V Clevenger
1Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Insights
Prolactin hormone enters the cell nucleus and interacts with cyclophilin B. This complex enhances gene expression by interacting with Stat5 and removing a repressor protein.
Area of Science:
- Molecular Biology
- Cell Biology
- Endocrinology
Background:
- Nuclear translocation of peptide hormones like prolactin is a known phenomenon.
- Prolactin interacts with cyclophilin B, an immunophilin protein.
Purpose of the Study:
- To investigate the role of cyclophilin B in prolactin's cellular functions.
- To elucidate the mechanism of prolactin-induced gene expression.
Main Methods:
- Studied prolactin-cyclophilin B interaction in cell cultures.
- Assessed the impact of cyclophilin B's peptidyl-prolyl isomerase activity.
- Analyzed the interaction with Stat5 and PIAS3.
Main Results:
- Cyclophilin B potentiates prolactin-induced proliferation, growth, and nuclear transport.
- The peptidyl-prolyl isomerase activity of cyclophilin B is crucial for these effects.
- The prolactin/cyclophilin B complex enhances Stat5 DNA-binding by removing PIAS3.
Conclusions:
- The intranuclear prolactin/cyclophilin B complex acts as a transcriptional inducer.
- This complex enhances prolactin-induced, Stat5-mediated gene expression.
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.