Retinoblastoma protein pRb

Shi SR, Cote RJ, Yang C, et al. Development of an optimal protocol for antigen retrieval a test battery approach exemplified with reference to the staining of retinoblastoma protein (pRB) in formalin-fixed paraffin sections. J. Pathol. 1996 179 347-352. 

Acetylation levels of histone and non-histone proteins are regulated upon DNA damage. Retinoblastoma protein pRb controls Gl-S phase transition and phosphorylation of pRb regulates it function. DNA damage induced acetylation of pRb near the phosphorylation sites prevents it phosphorylation and keep pRb in active form thereby leading to growth repression. DNA damage dependant association... 

Fig. 13.13. Domain structure of the retinoblastoma protein pRb. The phosphorylation sites (P) of pRb and the localization of the sequence sections necessary for interaction with viral oncoproteins and with the transcription factor E2F are shown. In addition, an oligomerization domain and a DNA binding domain can be identified.

The product of the retinoblastoma gene, the retinoblastoma protein pRb, functions as a switch for conversion of mitogenic and antimitogenic signals at the transcription... 

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). 

Substrate binding involves interactions with both the CDK and the cyclin. Whereas the CDK contacts mainly the residues surrounding the target Ser/Thr of the substrate, interactions between distinct sequence elements of the cyclin and the substrate have been shown to contribute to substrate specificity of cyclin-CDK complexes as well. The region of the cyclin responsible for this interaction is also involved in the binding of CDK inhibitors and other regulatory proteins such as the retinoblastoma protein, pRb (see Section 13.4.2). 

During the translocation, a part of the c-abl gene is fused to the first exon of the her gene (Fig. 14.5). The pl80BCR ABL hybrid protein demonstrates increased tyrosine kinase activity, and it has a changed subcellular location in that it is predominantly found in the cytosol, whereas c-Abl normally exerts its function in the nucleus. Nuclear c-Abl has been shown to have an important role in damage-induced apoptosis. It is found in a repressed state bound to retinoblastoma protein pRb during G0 and Gj. 

Shi SR, Liu G, Young L, Taylor GR. Development of an optimal antigen retrieval protocol for immunohistochemistry of retinoblastoma protein (pRB) in formalin fixed, paraffin sections based on comparison of different methods. Biotech Histochem. 2007 82 301. 

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