A Functional and Putative Physiological Role of Calcitriol in Patched1/Smoothened Interaction.
作者： Benedikt Linder , Susanne Weber , Kai Dittmann , Jerzy Adamski , Heidi Hahn
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摘要: The Patched1 (Ptch)-mediated inhibition of Smoothened (Smo) is still an open question. However, a direct Ptch/Smo interaction has been excluded, Smo modulators were identified, but the endogenous signal transmitting molecule remains undiscovered. Here, we demonstrate that calcitriol, hormonally active form vitamin D3, excellent candidate for transmission interaction. Our study reveals Ptch expression sufficient to release calcitriol from cell and inhibits action ciliary translocation by acting on site distinct 7-transmembrane domain or cysteine-rich domain. Moreover strongly synergizes with itraconazole (ITZ) in inhibition, which did not result elevated bioavailability due ITZ-mediated 24-hydroxylase rather compounds at level Smo. Together, suggest represents possible transmitter derivatives combined ITZ might be treatment option Hedgehog-associated cancers.
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