Cdc25B Functions As a Novel Coactivator for the Steroid Receptors

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 2001 Nov 2

PMID 11689696

Citations 14

Authors

Z Q Ma

Z Liu

E S Ngan

S Y Tsai

Affiliations

Soon will be listed here.

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.

Citing Articles

Comprehensive Analysis and Experimental Validation of a Novel Estrogen/Progesterone-Related Prognostic Signature for Endometrial Cancer.

Yu J, Yao H, Liu T, Wang D, Shi J, Yuan G J Pers Med. 2022; 12(6).

PMID: 35743699 PMC: 9225250. DOI: 10.3390/jpm12060914.

Neurogenic decisions require a cell cycle independent function of the CDC25B phosphatase.

Bonnet F, Molina A, Roussat M, Azais M, Bel-Vialar S, Gautrais J Elife. 2018; 7.

PMID: 29969095 PMC: 6051746. DOI: 10.7554/eLife.32937.

Regulation of steroid hormone receptors and coregulators during the cell cycle highlights potential novel function in addition to roles as transcription factors.

Zheng Y, Murphy L Nucl Recept Signal. 2016; 14:e001.

PMID: 26778927 PMC: 4714463. DOI: 10.1621/nrs.14001.

Ligand-based chemoinformatic discovery of a novel small molecule inhibitor targeting CDC25 dual specificity phosphatases and displaying in vitro efficacy against melanoma cells.

Capasso A, Cerchia C, Di Giovanni C, Granato G, Albano F, Romano S Oncotarget. 2015; 6(37):40202-22.

PMID: 26474275 PMC: 4741889. DOI: 10.18632/oncotarget.5473.

Kizuna is a novel mitotic substrate for CDC25B phosphatase.

Thomas Y, Peter M, Mechali F, Blanchard J, Coux O, Baldin V Cell Cycle. 2015; 13(24):3867-77.

PMID: 25558830 PMC: 4615109. DOI: 10.4161/15384101.2014.972882.

References

REYNOLDS R, Yem A, Wolfe C, Deibel Jr M, CHIDESTER C, Watenpaugh K . Crystal structure of the catalytic subunit of Cdc25B required for G2/M phase transition of the cell cycle. J Mol Biol. 1999; 293(3):559-68. DOI: 10.1006/jmbi.1999.3168. View

McMahon C, Suthiphongchai T, DiRenzo J, Ewen M . P/CAF associates with cyclin D1 and potentiates its activation of the estrogen receptor. Proc Natl Acad Sci U S A. 1999; 96(10):5382-7. PMC: 21868. DOI: 10.1073/pnas.96.10.5382. View

Ma Z, Tsai M, Tsai S . Suppression of gene expression by tethering KRAB domain to promoter of ER target genes. J Steroid Biochem Mol Biol. 1999; 69(1-6):155-63. DOI: 10.1016/s0960-0760(98)00154-x. View

Wu W, Fan Y, Kemp B, Walsh G, Mao L . Overexpression of cdc25A and cdc25B is frequent in primary non-small cell lung cancer but is not associated with overexpression of c-myc. Cancer Res. 1998; 58(18):4082-5. View

Tsai M, OMalley B . Molecular mechanisms of action of steroid/thyroid receptor superfamily members. Annu Rev Biochem. 1994; 63:451-86. DOI: 10.1146/annurev.bi.63.070194.002315. View

Korzus E, Torchia J, Rose D, Xu L, Kurokawa R, McInerney E . Transcription factor-specific requirements for coactivators and their acetyltransferase functions. Science. 1998; 279(5351):703-7. DOI: 10.1126/science.279.5351.703. View

Fauman E, Cogswell J, Lovejoy B, Rocque W, Holmes W, Montana V . Crystal structure of the catalytic domain of the human cell cycle control phosphatase, Cdc25A. Cell. 1998; 93(4):617-25. DOI: 10.1016/s0092-8674(00)81190-3. View

Fendrick J, Raafat A, Haslam S . Mammary gland growth and development from the postnatal period to postmenopause: ovarian steroid receptor ontogeny and regulation in the mouse. J Mammary Gland Biol Neoplasia. 2000; 3(1):7-22. DOI: 10.1023/a:1018766000275. View

Glass C, Rosenfeld M . The coregulator exchange in transcriptional functions of nuclear receptors. Genes Dev. 2000; 14(2):121-41. View

10.

Tzukerman M, Esty A, Danielian P, Parker M, Stein R, Pike J . Human estrogen receptor transactivational capacity is determined by both cellular and promoter context and mediated by two functionally distinct intramolecular regions. Mol Endocrinol. 1994; 8(1):21-30. DOI: 10.1210/mend.8.1.8152428. View

11.

Beato M, Herrlich P, Schutz G . Steroid hormone receptors: many actors in search of a plot. Cell. 1995; 83(6):851-7. DOI: 10.1016/0092-8674(95)90201-5. View

12.

Chen H, Lin R, Schiltz R, Chakravarti D, Nash A, Nagy L . Nuclear receptor coactivator ACTR is a novel histone acetyltransferase and forms a multimeric activation complex with P/CAF and CBP/p300. Cell. 1997; 90(3):569-80. DOI: 10.1016/s0092-8674(00)80516-4. View

13.

Hui R, CORNISH A, McClelland R, Robertson J, Blamey R, Musgrove E . Cyclin D1 and estrogen receptor messenger RNA levels are positively correlated in primary breast cancer. Clin Cancer Res. 1996; 2(6):923-8. View

14.

Mangelsdorf D, Thummel C, Beato M, Herrlich P, Schutz G, Umesono K . The nuclear receptor superfamily: the second decade. Cell. 1995; 83(6):835-9. PMC: 6159888. DOI: 10.1016/0092-8674(95)90199-x. View

15.

Neuman E, Ladha M, Lin N, Upton T, Miller S, DiRenzo J . Cyclin D1 stimulation of estrogen receptor transcriptional activity independent of cdk4. Mol Cell Biol. 1997; 17(9):5338-47. PMC: 232384. DOI: 10.1128/MCB.17.9.5338. View

16.

Heery D, Kalkhoven E, Hoare S, Parker M . A signature motif in transcriptional co-activators mediates binding to nuclear receptors. Nature. 1997; 387(6634):733-6. DOI: 10.1038/42750. View

17.

Xu L, Glass C, Rosenfeld M . Coactivator and corepressor complexes in nuclear receptor function. Curr Opin Genet Dev. 1999; 9(2):140-7. DOI: 10.1016/S0959-437X(99)80021-5. View

18.

Hoffmann I, Draetta G, Karsenti E . Activation of the phosphatase activity of human cdc25A by a cdk2-cyclin E dependent phosphorylation at the G1/S transition. EMBO J. 1994; 13(18):4302-10. PMC: 395357. DOI: 10.1002/j.1460-2075.1994.tb06750.x. View

19.

Furnari B, Blasina A, Boddy M, McGowan C, Russell P . Cdc25 inhibited in vivo and in vitro by checkpoint kinases Cds1 and Chk1. Mol Biol Cell. 1999; 10(4):833-45. PMC: 25205. DOI: 10.1091/mbc.10.4.833. View

20.

Jinno S, Suto K, Nagata A, Igarashi M, Kanaoka Y, Nojima H . Cdc25A is a novel phosphatase functioning early in the cell cycle. EMBO J. 1994; 13(7):1549-56. PMC: 394984. DOI: 10.1002/j.1460-2075.1994.tb06417.x. View