CDK inhibitors In a laboratory mutants have been identified in CDK4. Mutant A sh

Question

CDK inhibitors
In a laboratory mutants have been identified in CDK4.
Mutant A shows deletion of the kinase domain of Cdk4.
• Mutant B shows no degradation of Cyclin D1 by Cdk4.
Relative to the wild-type cells, which of these mutants (choose from mutant A or B) will show no cell proliferation? Explain why you selected this option over the other. CDK inhibitors
In a laboratory mutants have been identified in CDK4.
Mutant A shows deletion of the kinase domain of Cdk4.
• Mutant B shows no degradation of Cyclin D1 by Cdk4.
Relative to the wild-type cells, which of these mutants (choose from mutant A or B) will show no cell proliferation? Explain why you selected this option over the other. CDK inhibitors
In a laboratory mutants have been identified in CDK4.
Mutant A shows deletion of the kinase domain of Cdk4.
• Mutant B shows no degradation of Cyclin D1 by Cdk4.
Relative to the wild-type cells, which of these mutants (choose from mutant A or B) will show no cell proliferation? Explain why you selected this option over the other.

Explanation / Answer

Answer ) Mutant A does not show proliferation.

CDK4 and CDK6, are key regulators of the G1/S phase checkpoint. Cyclin D-CDK holoenzymes accumulate when resting cells are stimulated to proliferate by addition of growth factors. Their associated kinase activities are first detected in mid G1 phase and increase as cells approach the G1/S boundary. Removal of growth factors early in the G1 phase results in rapid decay of cyclin D-CDK activity and correlates with failure of the cells to enter the S phase. Removal of growth factors in late G1 also results in decay of cyclin D-CDK activity; however, it does not inhibit progression through the cell cycle. Furthermore, microinjection of cyclin D1 antibodies into cells during G1 prevents entry into S phase whereas injections at or after S phase have no effect. Thus, cyclin D-CDK complexes are essential for the G1 to S phase transition.

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