A constitutively active RAS mutation found in 30% of human cancers leads to uncontrolled cell proliferation because:

• A RAS is locked in the GDP-bound inactive conformation
• B RAS activates adenylyl cyclase, producing excess cAMP
• C RAS directly phosphorylates retinoblastoma protein
• D RAS cannot hydrolyse GTP to GDP due to impaired intrinsic GTPase activity ✓

Explanation

Oncogenic RAS mutations (most commonly Gly12→Val or Gly12→Asp) impair the GTPase activity of RAS, preventing hydrolysis of bound GTP to GDP; RAS-GTP remains permanently active, continuously stimulating the RAF→MEK→ERK MAPK cascade. Normal RAS is activated when GTP replaces GDP and is inactivated by its intrinsic GTPase. RAS does not directly affect cAMP or Rb.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.