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PNAS 99 (10): 6790-6795

Copyright © 2002 by the National Academy of Sciences.


The intranuclear prolactin/cyclophilin B complex as a transcriptional inducer

Michael A. Rycyzyn Charles V. Clevenger*

Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104

Accepted for publication March 19, 2002.

Received for publication October 26, 2001.

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.

* To whom reprint requests should be addressed. E-mail: clevengc{at}

Communicated by Peter C. Nowell, University of Pennsylvania School of Medicine, Philadelphia, PA

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