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

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Roy, Sougata 
Sipthorp, James 
Pramanik, Jhuma 
Hennrich, Marco L 

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 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.

Description

Keywords

3101 Biochemistry and Cell Biology, 32 Biomedical and Clinical Sciences, 31 Biological Sciences, 3204 Immunology, 3211 Oncology and Carcinogenesis, Urologic Diseases, Cancer, Prostate Cancer, 2 Aetiology, 2.1 Biological and endogenous factors, Generic health relevance, Cancer

Journal Title

iScience

Conference Name

Journal ISSN

2589-0042
2589-0042

Volume Title

24

Publisher

Elsevier BV

Rights

All rights reserved
Sponsorship
The ERC consolidator grant (ThDEFINE, Project ID: 646794) supported this study. SR was supported by an EIPOD fellowship and Ashoka University Individual Research grant for research visits. BM was supported by a CRUK Cancer Immunology grant (Ref. 20193).