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Molecular and Cellular Biology, December 2001, p. 8056-8067, Vol. 21, No. 23
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.23.8056-8067.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Cdc25B Functions as a Novel Coactivator for the Steroid Receptors

Zhi-Qing Ma, Zheng Liu, Elly S. W. Ngan, and Sophia Y. Tsai*

Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030

Received 5 July 2001/Returned for modification 4 August 2001/Accepted 4 September 2001

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.

* Corresponding author. Mailing address: Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030. Phone: (713) 798-6251. Fax: (713) 798-8227. E-mail: stsai{at}bcm.tmc.edu.

Molecular and Cellular Biology, December 2001, p. 8056-8067, Vol. 21, No. 23
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.23.8056-8067.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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