- Preventing the blocking action of Patched protein leads to activation of Cos-2, which dissociates itself from microtubules, activates Ci/Gli which binds to CBP (CREB- binding protein) and promotes transcription of target genes. Which one of the following
treatment of cells will mostly prevent Ci/Gli activated transcription in thecells?
(1) Small molecules which target Frizzled.
(2) Azepine, an inhibitor of y-secretase.
(3) Cyclopamine, which binds to hepta-helical bundle of Smoothened.
(4) Cdk blockers, which negatively regulate TGFβ- induced growth.
The treatment that would most likely prevent Ci/Gli activated transcription in the cells is:
(3) Cyclopamine, which binds to the hepta-helical bundle of Smoothened.
Explanation:
Cyclopamine is a well-known natural small molecule inhibitor of the Hedgehog (Hh) signaling pathway. It acts by directly binding to the hepta-helical transmembrane protein Smoothened (Smo), preventing its activation. Since Smoothened activity is required for downstream signaling that leads to activation of Ci/Gli transcription factors, cyclopamine effectively blocks the pathway upstream of Ci/Gli, thereby preventing their activation and subsequent transcription of target genes.
Patched (Ptch) normally inhibits Smoothened; when Ptch inhibition is relieved (such as by Hedgehog ligand), Smoothened becomes active and initiates the pathway that leads to Ci/Gli activation. Cyclopamine binding to Smoothened blocks this activation regardless of Ptch status, thus preventing Ci/Gli-mediated transcription.
Other options like small molecules targeting Frizzled affect Wnt signaling, not Hedgehog. Azepine inhibits γ-secretase, which is unrelated to the Hedgehog pathway. Cdk blockers involved in TGFβ signaling do not affect the Hedgehog pathway directly.
1 Comment
Kajal
November 7, 2025Option 3cyclopamine