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PMID: 11689696 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Cdc25B functions as a novel coactivator for the steroid receptors.

Molecular and cellular biology ·Vol. 21 ·No. 23 ·2001-12-00 ·Pages 8056-67

Ma ZQ, Liu Z, Ngan ES, Tsai SY

Abstract

We have previously demonstrated that overexpression of Cdc25B in transgenic mice resulted in mammary gland hyperplasia and increased steroid hormone responsiveness. To address how Cdc25B enhances the hormone responsiveness in mammary glands, we showed that Cdc25B stimulates steroid receptor-dependent transcription in transient transfection assays and in a cell-free assay with chromatin templates. Surprisingly, the effect of Cdc25B on steroid receptors is independent of its protein phosphatase activity in vitro. The direct interactions of Cdc25B with steroid receptors, on the other hand, were evidenced in in vivo and in vitro assays, suggesting the potential direct contribution of Cdc25B on the steroid receptor-mediated transcription. In addition, p300/CBP-associated factor and CREB binding protein were shown to interact and synergize with Cdc25B and further enhance its coactivation activity. Thus, we have uncovered a novel function of Cdc25B that serves as a steroid receptor coactivator in addition to its role as a regulator for cell cycle progression. This dual function might likely contribute to its oncogenic action in breast cancer.

MeSH Terms
Acetyltransferases/metabolism Animals Breast/metabolism CREB-Binding Protein Cell Cycle/physiology Cell Cycle Proteins/metabolism,pharmacology Cell Line Cell-Free System/metabolism Cyclin D1/metabolism Enzyme Activation/physiology Female Gene Expression Regulation/physiology Histone Acetyltransferases Humans Nuclear Proteins/metabolism Rats Receptors, Androgen/metabolism Receptors, Estrogen/metabolism Receptors, Glucocorticoid/metabolism Receptors, Progesterone/metabolism Receptors, Steroid/metabolism Saccharomyces cerevisiae Proteins Trans-Activators/metabolism Transcription Factors Transcription, Genetic/drug effects,physiology cdc25 Phosphatases/metabolism,pharmacology p300-CBP Transcription Factors
Chemicals
Cell Cycle Proteins Nuclear Proteins Receptors, Androgen Receptors, Estrogen Receptors, Glucocorticoid Receptors, Progesterone Receptors, Steroid Saccharomyces cerevisiae Proteins Trans-Activators Transcription Factors progesterone receptor B Cyclin D1 Acetyltransferases CREB-Binding Protein CREBBP protein, human Crebbp protein, rat Histone Acetyltransferases p300-CBP Transcription Factors p300-CBP-associated factor CDC25B protein, human cdc25 Phosphatases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Ma Z Q
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Liu Z
Ngan E S
Tsai S Y
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.21.23.8056-8067.2001
Published
2001-12-00
Pages
8056-67
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC99972
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.21.23.8056-8067.2001 PMC Full Text View journal details
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