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bioRxiv · 10.1101/800649

CLICK-enabled analogues reveal pregnenolone interactomes in cancer and immune cells

Roy, S.·Sipthorp, J.·Mahata, B.·Pramanik, J.·Hennrich, M. L.·Gavin, A.-C.·Ley, S. V.·Teichmann, S.
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Abstract

Pregnenolone (P5) promotes prostate cancer cell growth, and de novo synthesis of intratumoural P5 is a potential cause of development of castration-resistance. Immune cells can also synthesize P5 de novo. Despite its biological importance, little is known about P5s mode of actions, which appears to be context-dependent and pleiotropic. A comprehensive proteome-wide spectrum of P5-binding proteins that are involved in its trafficking and functionality remains unknown. Here, we describe an approach that integrates chemical biology for probe synthesis with chemoproteomics to map P5-protein interactions in live prostate cancer cells and murine CD8+ T cells. We subsequently identified P5-binding proteins potentially involved in P5-trafficking, and in P5s non-genomic action that may drive the promotion of castrate-resistance prostate cancer and regulate CD8+ T cell function. We envisage that this methodology could be employed for other steroids to map their interactomes directly in a broad range of living cells, tissues and organisms.

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Roy, S., Sipthorp, J., Mahata, B., Pramanik, J., Hennrich, M. L., Gavin, A.-C., Ley, S. V., Teichmann, S.. 2019-10-16. CLICK-enabled analogues reveal pregnenolone interactomes in cancer and immune cells. https://doi.org/10.1101/800649

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