RB protein, RB binds E2F and keeps it inactive The wild-type Retinoblastoma (Rb)
ID: 269375 • Letter: R
Question
RB protein, RB binds E2F and keeps it inactive The wild-type Retinoblastoma (Rb) protein functions to sequester the transcription factor E2F in the cytoplasm. At the appropriate time in dint Co the cell cycle (G1), a cyclin-dependent protein kinase/cyclin complex phosphorylates Rb, which then releases E2F so that it can enter the nucleus and act as a transcription factor to activate genes required for the S phase of the cell cycle. of cyclin-D-CDK and cyclin-E-CDK ...which activates RB and it releases E2F Would E2F be considered a proto- oncogene or a tumor suppressor? Explain using molecular examples in the pathway why you chose your answer. E2F binds to DNA and stimulates the transcription of genes required for DNA replication. a. DNA Promoter b. Are mutations that constantly release E2F considered to be dominant or recessive? Determine what affect each of the following Rb mutations would have on the progression through the cell cycle (decrease cell division, increase cell division or have no effect on the rate of cell division).Justify your answers by describing what happens molecularly in the cell in each situation. c. i. Rb is constitutively (constantly) phosphorylated. il. The phosphorylation site of Rb is mutated, thus it can never be phosphorylated is expressed at lower levels than normal. ii. The normal Rb proteinExplanation / Answer
a. E2F will be considered a proto oncogene as it stimulates cell cycle by binding to DNA and stimulating the transcription of genes required for DNA replication which occurs during S phase of cell cycle.
b. E2F is released by activation of Retinoblastoma protein, which is a tumour supressor gene. Only in the recessive state, RB mutants will lack any copy of the corresponding wild-type allele. Even if one allele of the RB gene is wild type, a functional RB protein will be formed.
c. i) Rb protein functions by binding the E2F transcription factor. Bound Rb prevents E2F from promoting the transcription of genes whose products are needed for DNAreplication. If Rb is constitutively phosphorylated, E2F would always able to promote S phase, and the arrest of normal cells in late G1 does not occur. Therefore, an increase in cell division will be observed.
ii) Rb in its unphosphorylated state binds to E2F and keeps it inactive. If phosphorylation site of Rb is mutated, E2F will not be released and genes required for DNA replication will not be expressed. Therefore, cell division will decrease.
iii) A reduction in expression level of Rb protein will cause an increase in cell division as there will not be sufficient Rb molecules to prevent E2F from promoting the cell cycle progression.
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