Promoters retinoblastoma protein

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). 

On the other hand, staurosporine analogues do not exhibit specificity for particular PKC isoenzymes, but they inhibit cPKC isoenzymes more potenly than n- and aPKCs. [98], UCN-01 (a 7-hydroxylated metabolite of staurosporine) blocks cells in the G1 phase by promoting accumulation of dephosphorylated retinoblastoma protein as a consequence of the inhibition of the activity of certain CDKs, downregulation of their partner cyclins and an increase in the expression of CDK inhibitor proteins [99],... 

The tumor-promoting activity of OA class compounds is dne to their inhibitory activity of protein phosphatases, which increases phosphorylation/activation of varions proteins involved in the signal transduction pathways regulating the cell cycle and cell transformation. ° Different effects of OA leading to transformation of cells were reported, such as induction of mitosis, ° ° cycle progression, " as well as cell proliferation genes and proto-oncogenes expression. " It has been demonstrated that OA induces the release and expression of tumor necrosis factor-a (TNF-a) and other cytokines, phosphorylation of the tnmor snppressors p53 and retinoblastoma pRb proteins, and activation and induction of the nnclear transcription factors, such as activator protein-1 (AP-1) andNF-KB. ... 

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