CLICK-enabled Analogues Reveal Pregnenolone Interactomes in Cancer and Immune Cells

Overview

Journal iScience

Publisher Cell Press

Date 2021 May 26

PMID 34036248

Citations 5

Authors

Sougata Roy

James Sipthorp

Bidesh Mahata

Jhuma Pramanik

Marco L Hennrich

Anne-Claude Gavin

Steven V Ley

Sarah A Teichmann

Affiliations

Soon will be listed here.

Abstract

Pregnenolone (P5) promotes prostate cancer cell growth, and synthesis of intratumoural P5 is a potential cause of development of castration resistance. Immune cells can also synthesize P5 . Despite its biological importance, little is known about P5's 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 P5's 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.

Citing Articles

Neuroactive Steroids, Toll-like Receptors, and Neuroimmune Regulation: Insights into Their Impact on Neuropsychiatric Disorders.

Balan I, Boero G, Chery S, McFarland M, Lopez A, Morrow A Life (Basel). 2024; 14(5).

PMID: 38792602 PMC: 11122352. DOI: 10.3390/life14050582.

Pregnenolone sulfate induces transcriptional and immunoregulatory effects on T cells.

El Hajj Y, Shahin T, Dieng M, Alshaikh M, Khair M, Manikandan V Sci Rep. 2024; 14(1):6782.

PMID: 38514798 PMC: 10958000. DOI: 10.1038/s41598-024-57327-0.

De novo steroidogenesis in tumor cells drives bone metastasis and osteoclastogenesis.

Sandor L, Huh J, Benko P, Hiraga T, Poliska S, Dobo-Nagy C Cell Rep. 2024; 43(3):113936.

PMID: 38489269 PMC: 10995766. DOI: 10.1016/j.celrep.2024.113936.

Local Effects of Steroid Hormones within the Bone Microenvironment.

Sandor L, Ragacs R, Gyori D Int J Mol Sci. 2023; 24(24).

PMID: 38139309 PMC: 10744126. DOI: 10.3390/ijms242417482.

CLICK-chemoproteomics and molecular dynamics simulation reveals pregnenolone targets and their binding conformations in Th2 cells.

Roy S, Roy S, Mahata B, Pramanik J, Hennrich M, Gavin A Front Immunol. 2023; 14:1229703.

PMID: 38022565 PMC: 10644475. DOI: 10.3389/fimmu.2023.1229703.

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