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Glucocorticoid Regulation of Cell Proliferation

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Steroid Hormones and Cell Cycle Regulation

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Abstract

Initiation of DNA replication in non-embryonic cells requires passage through an irreversible step in late Gl that has come to be called the restriction point. The restriction point was originally defined as the point in time beyond which inhibitors of protein synthesis could not prevent serum-stimulated cells from initiating DNA synthesis (Pardee, 1974). Prevailing wisdom defines the restriction point as irreversible activation of the cyclin E/Cdk2 complex at the Gl/S interphase. As discussed in previous chapters and in several excellent review articles (Sherr and Roberts, 1999; Ekholm and Reed, 2000; Vidal and Koff, 2000), activation of cyclin E/Cdk2 in late Gl begins with two events: 1) relief of transcriptional repression of the cyclin E promoter due to Cdk4-dependent phosphorylation of Rb-1, and the resulting dissociation of chromatin remodeling complexes; and 2) sequestration of Cip/Kip type Cdk2 inhibitors, which occurs as a result of accumulation of cyclin D/Cdk4/p27 and/or cyclin D/Cdk4/p21 complexes. Cdk4-dependent induction of cyclin E transcription and sequestration of the Cdk2 inhibitors Cipl and Kipl results in activation of Cdk2, which then promotes degradation of Kip 1 and further relieves Rb-1 dependent repression of the cyclin E and other promoters.

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  1. University of Texas Medical Branch, Galveston, TX, 77555-1048, USA

    E. Aubrey Thompson

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  1. University of Miami School of Medicine, USA

    Kerry L. Burnstein

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Thompson, E.A. (2002). Glucocorticoid Regulation of Cell Proliferation. In: Burnstein, K.L. (eds) Steroid Hormones and Cell Cycle Regulation. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0965-3_8

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  • DOI: https://doi.org/10.1007/978-1-4615-0965-3_8

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