A tumor suppressor gene product normally sequesters E2F transcription factors by binding them through a 'pocket domain', thereby preventing S-phase entry. Loss of this protein's function is a hallmark of which type of carcinogenesis?

• A Rb protein loss leading to unrestricted E2F-driven transcription ✓
• B p53 loss leading to failure of apoptosis
• C PTEN loss leading to PI3K pathway activation
• D VHL loss leading to HIF-1α stabilization

Explanation

The retinoblastoma protein (pRb) contains a 'pocket domain' that binds and sequesters E2F transcription factors during G1. When pRb is phosphorylated by CDK4/6-cyclin D1 complexes, E2F is released to drive S-phase gene transcription. Loss-of-function mutations in RB1 (both alleles) constitutively activate E2F, a central mechanism in retinoblastoma and many other cancers. The other proteins act through distinct non-E2F pathways.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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