Molecular biology and genetics: CDK4/6 inhibition and Rb: practice question

A Biochemistry question in the style of the NEET PG paper. Answer it first, then read why the right option is right and why each of the others is wrong.

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Biochemistry · Molecular biology and genetics: CDK4/6 inhibition and Rb

Sample item

A woman with hormone receptor-positive breast cancer is started on palbociclib, a CDK4/6 inhibitor. Which event is blocked, arresting cells in G1?

AActivation of p53 by ATM kinase after a double-strand DNA breakBDegradation of cyclin B at the end of mitosis by the anaphase complexCPhosphorylation of Rb protein, which would release E2F transcription factorsDAttachment of spindle microtubules to kinetochores during prometaphase

Original practice item, not a recalled exam question. Nothing here is recorded.

The answer and the reasoning

C. Phosphorylation of Rb protein, which would release E2F transcription factors

Cyclin D with CDK4/6 phosphorylates Rb, which releases E2F and permits transcription of S-phase genes. Palbociclib prevents this phosphorylation, so Rb stays bound to E2F and cells arrest in G1. It is used with endocrine therapy in hormone receptor-positive disease.

Option by option

A. Activation of p53 by ATM kinase after a double-strand DNA break
ATM activation of p53 follows DNA damage and is not the target of this drug.
B. Degradation of cyclin B at the end of mitosis by the anaphase complex
Cyclin B degradation concerns exit from mitosis, not the G1 to S transition.
C. Phosphorylation of Rb protein, which would release E2F transcription factors (correct)
Correct. Blocking CDK4/6 keeps Rb unphosphorylated and E2F inactive.
D. Attachment of spindle microtubules to kinetochores during prometaphase
Spindle attachment occurs in mitosis and is the target of taxanes and vinca alkaloids.

Source note: Original NextPrep sample item — pending expert review. This item is original practice material awaiting independent expert review, so confirm important facts in a standard textbook.

Questions about this Biochemistry question

What is the answer to this Biochemistry question?

The best answer is C, Phosphorylation of Rb protein, which would release E2F transcription factors. Cyclin D with CDK4/6 phosphorylates Rb, which releases E2F and permits transcription of S-phase genes.

Why is "Activation of p53 by ATM kinase after a double-strand DNA break" not the answer?

ATM activation of p53 follows DNA damage and is not the target of this drug.

Why is "Degradation of cyclin B at the end of mitosis by the anaphase complex" not the answer?

Cyclin B degradation concerns exit from mitosis, not the G1 to S transition.

Why is "Attachment of spindle microtubules to kinetochores during prometaphase" not the answer?

Spindle attachment occurs in mitosis and is the target of taxanes and vinca alkaloids.

What concept does this question test?

It tests Molecular biology and genetics: CDK4/6 inhibition and Rb in Biochemistry. Palbociclib prevents this phosphorylation, so Rb stays bound to E2F and cells arrest in G1. It is used with endocrine therapy in hormone receptor-positive disease.

How hard is this question?

We tag it as a multi-step question: it asks you to combine more than one idea. The tag is our own editorial judgement, not an official difficulty rating, so read the reason for every option, not only the answer.

How should I study Molecular biology and genetics: CDK4/6 inhibition and Rb?

Build one table of enzyme deficiency, disease, inheritance and key finding, then revise it by spaced recall. Then use the flashcards and the other Biochemistry questions on this site to test what stuck.

Is this a real NEET PG question?

No. It is an original practice item (editorial status: sample, version 1). NextPrep does not publish recalled or leaked questions, and independent faculty review of this item has not been completed yet, so confirm important facts in a standard textbook.