Retinoblastoma protein , cell cycle regulation

Herwig, S. Strauss, M. (1997) The retinoblastoma protein a master regulator of cell cycle, differentiation and apoptosis. Eur. J. Biochem. 246, 581-601. 

Cobrinik D, Dowdy SF, Hinds PW et al. The retinoblastoma protein and the regulation of cell cycling. TIBS 1992 17 312. 

The RB gene encodes a transcriptional co-repressor which forms a complex with the cell-cycle-regulating transcription factor E2F (members of the E2F family of transcriptional activators control the genes involved in the Gj/S transition and in DNA replication 20 see Chapter 12). The RB—E2F transcriptional complex contains additional factors, such as the histone deacetylase, HDACl, which facilitates access of the transcriptional complex to E2F-responsive gene promoters, such as the cycKn E promoter. pRB and HDACl act in concert and repress the cyclin E promoter. i Hence the retinoblastoma protein (pRB) is a tumour-suppressor that represses gene expression in concert with a histone deacetylase, by modulating the architecture of chromatin (Fig. 15.4). The pRB- E2F transcriptional complex also represses transcription of RNA polymerase III22 (see also Chapter 9). 

Figure 21.16 k diagram of the mechanism by which retinoblastoma protein (Rb) regulates transcription factor activity. The rb protein binds to the transcription factor, which forms a complex in which the transcription factor for three genes is inactive. Phosphorylation of Rb by a cell division cycle kinase results in dissociation of transcription factor from the complex and hence activation. 

We have examined how cells maintain close control of CDK activity, but how does the activity of CDK control the cell cycle The list of target proteins that CDKs are known to act upon continues to grow, and much remains to be learned. But we can see a general pattern behind CDK regulation by inspecting the effect of CDKs on the structures of laminin and myosin and on the activity of retinoblastoma protein. 

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