Of the following mutations, which are likely to cause cell-cycle arrest? If you predict a cell-cycle arrest, indicate whether the cell will arrest in early G1, late G1, or G2. Explain your answers

Question

A. a mutation in a gene encoding a cell-surface mitogen receptor that makes the receptor active even in the absence of the mitogen
B. a mutation that destroyed the kinase activity of S-Cdk
C. a mutation that allowed G1-Cdk to be active independently of its phosphorylation status
D. a mutation that removed the phosphorylation sites on the Rb protein
E. a mutation that inhibited the activity of Rb

Answer 1

B and D are likely to cause cell-cycle arrest.
A. Because ligand-independent activation of a mitogen receptor will probably make the cell divide when it otherwise might not, this mutation is unlikely to cause a cell-cycle arrest.
B. This mutation is likely to cause cell-cycle arrest in late G1. Without S-Cdk activity, the cells will probably be unable to enter S phase.
C. Phosphorylation-independent activity of G1-Cdk is unlikely to lead to cell-cycle arrest; the cells should progress through the cycle, although the kinetics and fine regulation of the cycle may be altered.
D. This mutation is likely to cause cell-cycle arrest in early G1. Unphosphorylated Rb will inhibit the transcription of genes required for progression through G1 and into S phase. This inhibition is normally released on phosphorylation of Rb. If Rb cannot be phosphorylated, it will always inhibit transcription of these genes, leading to arrest in early G1.
E. If Rb is inactivated by a mutation, cells will be more likely to divide in the absence of extracellular mitogens, which is the opposite of a cell-cycle arrest.