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E2F1 is crucial for E2F-dependent apoptosis - Coursework Example

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E2F1 is crucial for E2F-dependent apoptosis

These proteins have the ability to function at all parts of the cell. These genes also lead to the discovery of familial cancer syndromes. About 50 tumor suppressor genes were catalogued and pRb and p53 proteins were found to have preeminent importance in the human tumor pathogenesis. pRb is closely co ordinate with the cell cycle. pRb hyperphosphorylation occurs when the cells pass the M/G1 transition at the R point. pRb contains atleast 16 different sites for phosphorylation. Thus it proves that pRb is the molecular governor of the R point transition. After the findings that the DNA tumor-virus encoded oncoproteins can disrupt the regulation of cell growth, the importance of learning pRb became important. It was also found that 3 DNA tumor virus oncoproteins, though they are structurally unrelated, they targeted the pRb. pRb inactivation can be done in four pathways. Interaction with viral proteins, phosphorylation, gene mutation and caspase mediated deregulation. The binding of the onco proteins at the site of pRb also promote cellular proliferation. The cell cycle dependent transcription was associated with the co ordination of the pRb and the E2F as the central mechanism. The pRB which are also called as rocket proteins helps to silence the E2F regulated promoters. The complexes between the pRb and the E2F family members were found to be formed at various phases of the cell cycle. The pRb/E2F complex helps to regulate growth arrest and cell cycle reentry. This association is released by phosphorylation of the pRb by the cyclin dependent kinase. In the absence of pRb protein, the cell death was found to be higher. Hence the effect of pRb on the apoptosis was studied. The E2F protein and the pRb complex formation and dissociation was extensively studied. Apoptosis in the absence of the pRb was found to be dependent on the activity of E2F1. The cell cycle progression is dependent upon the release of the E2F mediated by the phosphorylation of pRb. The E2Fs contain a distinct domain at the C terminus which is more important for protein binding. The E2F1 mediated apoptosis is ascribed to two mechanisms both p53- dependent and p53- independent. When there occurs any DNA damage during the G0 and G1 phases, the p 53 tumor suppressor proteins induces apoptosis. E2F1 can proliferate and arrest the cell cycle at any stage. Thus it acts as both positive and negative regulator. The hypophosphorylation of pRb binds to the E2Fs and activates it through negative regulation. Thus E2Fs expression on regulated genes increases. Since E2F1 and E2F3 loss can induce apoptosis, this became the key factor in the study of human cancer. E2F transcription factor are associated with a number of promoters on the cell cycle at G1. These E2Fs are bound by many pocket proteins. These pocket proteins are the pRb proteins. When these pRbs undergo hyperphosphorylation, they lose their grip on E2Fs and they stimulate the transcription of the genes. The viral onco proteins target the pRb and they mimic pRb hyperhosphorylation and prevent pRb from binding to the E2Fs. E2Fs is a heterodimeric protein composed of E2F1, 2, 3, 4, 5 and 6 sub units. In this report, the ability of E2F3 to trigger apoptosis in vivo was analyzed and concluded that E2F3 deregulation will trigger apoptosis. It was also concluded that E2F1 and E2F3 association is required for ...Show more


E2F1 is crucial for E2F-dependent apoptosis Cell cycle regulates the cell proliferation and they must divide to enter the mitotic state. Before entering the mitotic phase, the cell must pass through a number of check points. Retinoblastoma protein (pRb) plays an important role in the epithelial cell differentiation and viability apart from this they also act as positive transcriptional co regulators…
Author : michelwalsh
E2F1 is crucial for E2F-dependent apoptosis essay example
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