Ophthalmology · Retina (Vascular Disorders, Detachment, Macular Disorders, Retinoblastoma)

The RB1 gene product (pRb) normally restrains the cell cycle by binding to which transcription factor, preventing S-phase entry?

  • A E2F family of transcription factors
  • B p53
  • C c-Myc oncoprotein
  • D PCNA (proliferating cell nuclear antigen)
Correct answer: A. E2F family of transcription factors

Explanation

The retinoblastoma protein (pRb) is a tumor suppressor that, in its hypophosphorylated (active) form, binds and inhibits the E2F family of transcription factors. E2F proteins, when free, transcriptionally activate genes required for S-phase entry (DNA synthesis). In normal cells, cyclin D-CDK4/6 phosphorylates pRb, releasing E2F and permitting cell cycle progression. Loss-of-function mutations in both RB1 alleles (Knudson's two-hit hypothesis) lead to constitutively free E2F and unregulated proliferation. Retinoblastoma uniquely arises in Rb-deficient cells because photoreceptor precursors in developing retina depend on this pathway for cell cycle exit during differentiation.

Reference: Khurana Comprehensive Ophthalmology, 7th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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