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• W3158429811 abstract "•Developed four functional click-enabled analogues of pregnenolone (P5)•Chemoproteomics prioritizes 62 P5 target proteins in live cancer and immune cells•These include shared and distinct biochemical role of P5 in cancer and immune cells•P5 activity in cancer and immune cells is mediated through non-genomic pathways 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. 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. Pregnenolone (P5) is the first bioactive steroid hormone and precursor of all other steroid hormones in steroid biosynthesis (steroidogenesis) pathways. P5 is synthesized from cholesterol by the enzyme CYP11A1 inside the mitochondria of steroidogenic cells (Miller and Auchus, 2011Miller W.L. Auchus R.J. The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders.Endocr. Rev. 2011; 32: 81-151Crossref PubMed Scopus (1202) Google Scholar). A high capacity for P5 biosynthesis has been reported in adrenal tissue, gonads, and placenta. Extra-adrenal and extra-gonadal P5 synthesis (also known as local steroidogenesis) has been reported in lymphocytes (Jia et al., 2013Jia Y. Domenico J. Takeda K. Han J. Wang M. Armstrong M. Reisdorph N. O’Connor B.P. Lucas J.J. Gelfand E.W. Steroidogenic enzyme Cyp11a1 regulates Type 2 CD8+ T cell skewing in allergic lung disease.PNAS. 2013; 110: 8152-8157Crossref PubMed Scopus (19) Google Scholar; Wang et al., 2013Wang M. Ramirez J. Han J. Jia Y. Domenico J. Seibold M.A. Hagman J.R. Gelfand E.W. The steroidogenic enzyme Cyp11a1 is essential for development of peanut-induced intestinal anaphylaxis.J. Allergy Clin. Immunol. 2013; 132: 1174-1183.e8Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar; Mahata et al., 2014Mahata B. Zhang X. Kolodziejczyk A.A. Proserpio V. Haim-Vilmovsky L. Taylor A.E. Hebenstreit D. Dingler F.A. Moignard V. Göttgens B. et al.Single-cell RNA sequencing reveals T helper cells synthesizing steroids de novo to contribute to immune homeostasis.Cell Rep. 2014; 7: 1130-1142Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar), adipocytes (Li et al., 2014Li J. Daly E. Campioli E. Wabitsch M. Papadopoulos V. De novo synthesis of steroids and oxysterols in adipocytes.J. Biol. Chem. 2014; 289: 747-764Abstract Full Text Full Text PDF PubMed Scopus (56) Google Scholar), the nervous system (Baulieu, 1998Baulieu E.E. Neurosteroids: a novel function of the brain.Psychoneuroendocrinology. 1998; 23: 963-987Crossref PubMed Scopus (494) Google Scholar), tumors (Locke et al., 2008Locke J.A. Guns E.S. Lubik A.A. Adomat H.H. Hendy S.C. Wood C.A. Ettinger S.L. Gleave M.E. Nelson C.C. Androgen levels increase by intratumoral de novo steroidogenesis during progression of castration-resistant prostate cancer.Cancer Res. 2008; 68: 6407-6415Crossref PubMed Scopus (602) Google Scholar), and tumour-infiltrating immune cells (Mahata et al., 2020Mahata B. Pramanik J. van der Weyden L. Polanski K. Kar G. Riedel A. Chen X. Fonseca N.A. Kundu K. Campos L.S. et al.Tumors induce de novo steroid biosynthesis in T cells to evade immunity.Nat. Commun. 2020; 11: 3588Crossref PubMed Scopus (15) Google Scholar). The role played by this local P5 synthesis is poorly understood (Miller, 2017Miller W.L. Steroidogenesis: Unanswered questions.Trends Endocrinol. Metab. 2017; 28: 771-793Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar), particularly in pathologies such as cancer. In prostate cancer and melanoma P5 promotes tumor growth (Grigoryev et al., 2000Grigoryev D.N. Long B.J. Njar V.C. Brodie A.H. Pregnenolone stimulates LNCaP prostate cancer cell growth via the mutated androgen receptor.J. Steroid Biochem. Mol. Biol. 2000; 75: 1-10Crossref PubMed Scopus (59) Google Scholar; Mahata et al., 2020Mahata B. Pramanik J. van der Weyden L. Polanski K. Kar G. Riedel A. Chen X. Fonseca N.A. Kundu K. Campos L.S. et al.Tumors induce de novo steroid biosynthesis in T cells to evade immunity.Nat. Commun. 2020; 11: 3588Crossref PubMed Scopus (15) Google Scholar), whereas in glioma it restricts tumor growth (Xiao et al., 2014Xiao X. Chen L. Ouyang Y. Zhu W. Qiu P. Su X. Dou Y. Tang L. Yan M. Zhang H. et al.Pregnenolone, a cholesterol metabolite, induces glioma cell apoptosis via activating extrinsic and intrinsic apoptotic pathways.Oncol. Lett. 2014; 8: 645-650Crossref PubMed Scopus (10) Google Scholar). The mode of action of P5 in tumors is incompletely understood. In the nervous system, P5 is known to regulate synapse formation, promote outgrowth of neurites, enhance myelinization (Mellon, 2007Mellon S.H. Neurosteroid regulation of central nervous system development.Pharmacol. Ther. Neurosteroids Spec. Issue. 2007; 116: 107-124Crossref PubMed Scopus (157) Google Scholar), and improve cognitive and memory function (Mayo et al., 2001Mayo W. Le Moal M. Abrous D.N. Pregnenolone sulfate and aging of cognitive functions: behavioral, neurochemical, and morphological investigations.Horm. Behav. 2001; 40: 215-217Crossref PubMed Scopus (37) Google Scholar). During immune response against helminth parasite infection T helper cells synthesize P5 to restore immune homeostasis (Mahata et al., 2014Mahata B. Zhang X. Kolodziejczyk A.A. Proserpio V. Haim-Vilmovsky L. Taylor A.E. Hebenstreit D. Dingler F.A. Moignard V. Göttgens B. et al.Single-cell RNA sequencing reveals T helper cells synthesizing steroids de novo to contribute to immune homeostasis.Cell Rep. 2014; 7: 1130-1142Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar). Up to now, we do not have a proteome-wide description of the P5-interacting molecules in any living cells. Traditionally, steroid hormones have been considered to act by regulating transcription (Mazaira et al., 2018Mazaira G.I. Zgajnar N.R. Lotufo C.M. Daneri-Becerra C. Sivils J.C. Soto O.B. Cox M.B. Galigniana M.D. The nuclear receptor field: a historical overview and future challenges.Nucl. Receptor Res. 2018; 5Crossref PubMed Google Scholar). However, rapid activity of steroid hormones can be mediated by non-genomic pathways (Lösel and Wehling, 2003Lösel R. Wehling M. Nongenomic actions of steroid hormones.Nat. Rev. Mol. Cell Biol. 2003; 4: 46-55Crossref PubMed Scopus (665) Google Scholar). Non-genomic pathways appear to mediate P5 activity (Weng and Chung, 2016Weng J.-H. Chung B. Nongenomic actions of neurosteroid pregnenolone and its metabolites.Steroids Proc. 9th Int. Meet. Rapid Responses Steroid Horm. (RRSH 2015). 2016; 111: 54-59Google Scholar) in a cell-type-specific and context-dependent manner, indicating a need for proteome-wide studies to map the full spectrum of P5 functions. Here, we have developed a chemical biology method to generate clickable P5-analogues for use in living cells. Exploiting these P5 probes in combination with quantitative mass spectrometry, we profiled global P5-protein interactions directly in two distinct cell types: a steroid-sensitive cell line derived from a metastatic prostate cancer patient (i.e. LNCaP) and de novo P5-producing mouse CD8+ T cells. Altogether, we identified 62 high-confidence P5-binding proteins and about 387 potential P5-binding proteins localized in the nucleus, mitochondria, and endoplasmic reticulum (ER). These proteins include receptors, channels, transporters, and cytoskeletal proteins such as vimentin and enzymes, of which many represent novel interactions. Overall, we identified P5-binding proteins potentially involved in inter- and intra-cellular P5-trafficking and P5's non-genomic action that drives prostate cancer promotion of castration-resistance and mediates CD8+ T cell regulation. This study unravels prospective routes for understanding pregnenolone biochemistry in different cellular contexts such as prostate cancer progression and immune cell regulation. We demonstrate a general methodology to decipher P5-biochemistry in de novo steroidogenic and steroid-responsive cells or tissues. To capture the P5 interactome in living cells, we utilize photoaffinity labeling combined with enrichment of tagged proteins using a bioorthogonal handle. This strategy required modification of the P5 core, while also retaining the primary pharmacology of P5. A minimalist photoaffinity enrichment linker has been introduced to kinase inhibitors to map their interactomes (Li et al., 2013Li Z. Hao P. Li L. Tan C.Y.J. Cheng X. Chen G.Y.J. Sze S.K. Shen H.-M. Yao S.Q. Design and synthesis of minimalist terminal alkyne-containing diazirine photo-crosslinkers and their incorporation into kinase inhibitors for cell- and tissue-based proteome profiling.Angew. Chem. Int. Edition. 2013; 52: 8551-8556Crossref PubMed Scopus (181) Google Scholar). The linker utilizes a diazirine as the UV-induced cross-linking agent and an alkyne tag, upon which bioorthogonal chemistry could be performed after photoaffinity labeling to enrich tagged proteins using azide-biotin (Figure 1A). The linker was selected due to its small size, reducing the risk of the tag altering the P5 interactome and due to the proven effectiveness of this type of approach (Hulce et al., 2013Hulce J.J. Cognetta A.B. Niphakis M.J. Tully S.E. Cravatt B.F. Proteome-wide mapping of cholesterol-interacting proteins in mammalian cells.Nat. Methods. 2013; 10: 259-264Crossref PubMed Scopus (248) Google Scholar; Li et al., 2013Li Z. Hao P. Li L. Tan C.Y.J. Cheng X. Chen G.Y.J. Sze S.K. Shen H.-M. Yao S.Q. Design and synthesis of minimalist terminal alkyne-containing diazirine photo-crosslinkers and their incorporation into kinase inhibitors for cell- and tissue-based proteome profiling.Angew. Chem. Int. Edition. 2013; 52: 8551-8556Crossref PubMed Scopus (181) Google Scholar; Weng et al., 2013Weng J.-H. Liang M.-R. Chen C.-H. Tong S.-K. Huang T.-C. Lee S.-P. Chen Y.-R. Chen C.-T. Chung B. Pregnenolone activates CLIP-170 to promote microtubule growth and cell migration.Nat. Chem. Biol. 2013; 9: 636-642Crossref PubMed Scopus (33) Google Scholar). With these considerations in mind, we synthesized molecule 8 (Figure 1B) to conjugate to P5 at three different positions to ensure maximum coverage of molecular space and avoid preclusion of binding by a particular linker. The P5-derived probes were named P5-A, P5-B1, P5-B2, and P5-C (Figures 1C and S1) and tested for bioactivity and cell permeability. P5 is known to stimulate LNCaP prostate cancer cell growth (Grigoryev et al., 2000Grigoryev D.N. Long B.J. Njar V.C. Brodie A.H. Pregnenolone stimulates LNCaP prostate cancer cell growth via the mutated androgen receptor.J. Steroid Biochem. Mol. Biol. 2000; 75: 1-10Crossref PubMed Scopus (59) Google Scholar) and inhibit U87MG glioma cell growth (Xiao et al., 2014Xiao X. Chen L. Ouyang Y. Zhu W. Qiu P. Su X. Dou Y. Tang L. Yan M. Zhang H. et al.Pregnenolone, a cholesterol metabolite, induces glioma cell apoptosis via activating extrinsic and intrinsic apoptotic pathways.Oncol. Lett. 2014; 8: 645-650Crossref PubMed Scopus (10) Google Scholar). To test the biological activity of the P5-A, P5-B1, P5-B2, and P5-C we performed cell viability assays using the LNCaP and U87MG cells. Although LNCaP cells show increased cell viability in the presence of P5, it has a cytotoxic effect on U87MG cells (Figure 2A). For LNCaP cells, only two nM of P5-A is sufficient to induce a 4-fold increase in cell proliferation, which corresponds to the effect of 20 nM of P5 (Figure S2A). However, at higher concentration of P5-A, there is decrease in cell viability. For P5-C, cell viability follows exactly the same pattern as for P5. In both cases, cell proliferation gradually increases from 3-fold to 4-fold between 2 nM and 20 nM concentration of P5-C or P5 (Figure 2A top panel). P5-B1 and P5-B2 (although slightly better than P5-B1) can only induce cell growth to 3-fold corresponding to the highest concentration i.e. 20 nM (Figure S2A). In summary, P5-C shows the best retention of the parental pharmacology of P5. U87MG cells are known to undergo apoptosis in the presence of P5. All four probes induced apoptosis at lower concentrations than the parental P5. P5-B2 showed the highest apoptotic activity with 3-fold reduction in cell viability at only 20 μM concentration; the same concentration of P5 does not induce any significant reduction of cells. In contrast, 100 μM of all the probes produces a significant reduction in cell number that also corresponds to the cell viability at 100 μM in the cells with P5 (Figure 2A bottom panel and Figure S2B). P5 inhibits murine T helper cell proliferation and B cell class switching (Mahata et al., 2014Mahata B. Zhang X. Kolodziejczyk A.A. Proserpio V. Haim-Vilmovsky L. Taylor A.E. Hebenstreit D. Dingler F.A. Moignard V. Göttgens B. et al.Single-cell RNA sequencing reveals T helper cells synthesizing steroids de novo to contribute to immune homeostasis.Cell Rep. 2014; 7: 1130-1142Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar). To test whether addition of the linker retains the biological activity of P5 in this context, we performed T helper cell proliferation assays and B cell immunoglobulin class switching assays in the presence of P5-A, P5-B1, P5-B2, and P5-C. The presence of P5 in the in vitro Th2 culture conditions significantly restricts cell proliferation compared with vehicle-only-treated conditions (Figure 2B, right-side panel). We found that P5-C, like P5, inhibits T cell proliferation (Figure 2B, left-side panel). P5-A, P5-B1, and P5-B2 showed similar properties (Figure S3A). In immunoglobulin class-switching experiments we observed that the P5-C and the other P5 probes are equally efficient as P5 (Figures 2C and S3B). CAP-Gly domain containing linker protein 1 or cytoplasmic linker protein 1 (CLIP1, also known as CLIP170) was previously reported to be a specific P5 binding protein in zebrafish and human (Weng et al., 2013Weng J.-H. Liang M.-R. Chen C.-H. Tong S.-K. Huang T.-C. Lee S.-P. Chen Y.-R. Chen C.-T. Chung B. Pregnenolone activates CLIP-170 to promote microtubule growth and cell migration.Nat. Chem. Biol. 2013; 9: 636-642Crossref PubMed Scopus (33) Google Scholar). To test whether our P5 probes mimic P5's binding activity with CLIP1, we expressed CLIP1 ectopically in HEK293 cells, and the lysate was used to analyze the CLIP1 binding affinity of the P5 probes. All the P5 probes were able to pull down the CLIP1 protein from the lysate with similar efficiency (Figures 2D and S4). Unlabeled P5 was able to compete out P5-C binding to the CLIP1 protein, indicating P5-C's ability to capture P5 interactome (Figure 2D) and clearly reflecting its ability to bind known P5-binding proteins. To confirm the cell permeability of P5-C, we cultured LNCaP cells in the presence or absence of P5-C followed by CLICK reaction with an azide-bearing fluorophore. Subsequent fluorescence microscopy showed that the P5-C could enter live LNCaP cells (Figure 2E). To ascertain that P5-C can mimic P5's binding ability, LNCaP cell extracts were incubated with P5-C in the presence or absence of competing amounts of P5. In parallel, two other controls were performed, one without UV irradiation and another without P5-C being present. All the samples were loaded onto an SDS-PAGE gel and silver stained (Figure 3A). Ten-fold excess of P5 compared with P5-C was able to effectively compete out the P5-C binding, confirming our earlier observation (with CLIP1). P5-C captures P5-interacting proteins in a complex protein mixture. The samples without UV treatment and the neutravidin beads did not show any significant binding. The above benchmarking and quality control results confirmed the P5-C molecule as true analogue of P5 and an ideal probe to study in vivo P5 interactomes. LNCaP cells are steroid-sensitive prostate cancer cell line, which has been used widely as a model of human prostate cancer and was previously shown to respond to P5 (Grigoryev et al., 2000Grigoryev D.N. Long B.J. Njar V.C. Brodie A.H. Pregnenolone stimulates LNCaP prostate cancer cell growth via the mutated androgen receptor.J. Steroid Biochem. Mol. Biol. 2000; 75: 1-10Crossref PubMed Scopus (59) Google Scholar). Prostate cancer cells and tumour-infiltrating T cells produce P5 de novo, which can cause autocrine and paracrine responses in the tumor microenvironment (Locke et al., 2008Locke J.A. Guns E.S. Lubik A.A. Adomat H.H. Hendy S.C. Wood C.A. Ettinger S.L. Gleave M.E. Nelson C.C. Androgen levels increase by intratumoral de novo steroidogenesis during progression of castration-resistant prostate cancer.Cancer Res. 2008; 68: 6407-6415Crossref PubMed Scopus (602) Google Scholar; Mahata et al., 2020Mahata B. Pramanik J. van der Weyden L. Polanski K. Kar G. Riedel A. Chen X. Fonseca N.A. Kundu K. Campos L.S. et al.Tumors induce de novo steroid biosynthesis in T cells to evade immunity.Nat. Commun. 2020; 11: 3588Crossref PubMed Scopus (15) Google Scholar). Therefore, we proceeded to use these two cell types to reveal the proteome-wide map of P5-interacting proteins. We also used a published cholesterol interactome dataset (Hulce et al., 2013Hulce J.J. Cognetta A.B. Niphakis M.J. Tully S.E. Cravatt B.F. Proteome-wide mapping of cholesterol-interacting proteins in mammalian cells.Nat. Methods. 2013; 10: 259-264Crossref PubMed Scopus (248) Google Scholar) to show the overlap with sterol-binding proteins in our P5 interactome (Table 1 and Figure S9).Table 1The details of 62 “P5-binding proteins”Gene namesOrganismProtein namesACSL1aAlso known to interact with sterol in a different cell type, # present in both human cancer and mouse immune cells. 38 P5 target proteins in LNCaP prostate cell line from Homo sapiens and 25 P5 target proteins from CD8+ immune cell from Mus musculus.Homo sapiens (Human)Long-chain-fatty-acid--CoA ligase 1ACTN4Homo sapiens (Human)Actinin alpha 4 isoform 3AIFM1aAlso known to interact with sterol in a different cell type, # present in both human cancer and mouse immune cells. 38 P5 target proteins in LNCaP prostate cell line from Homo sapiens and 25 P5 target proteins from CD8+ immune cell from Mus musculus.Homo sapiens (Human)Apoptosis-inducing factor 1, mitochondrialALDH3A2aAlso known to interact with sterol in a different cell type, # present in both human cancer and mouse immune cells. 38 P5 target proteins in LNCaP prostate cell line from Homo sapiens and 25 P5 target proteins from CD8+ immune cell from Mus musculus.Homo sapiens (Human)Fatty aldehyde dehydrogenaseATL3Homo sapiens (Human)Atlastin-3CAND1Homo sapiens (Human)Cullin-associated NEDD8-dissociated protein1CERS2Homo sapiens (Human)Ceramide synthase 2CKAP4aAlso known to interact with sterol in a different cell type, # present in both human cancer and mouse immune cells. 38 P5 target proteins in LNCaP prostate cell line from Homo sapiens and 25 P5 target proteins from CD8+ immune cell from Mus musculus.Homo sapiens (Human)Cytoskeleton-associated protein 4CPT1AaAlso known to interact with sterol in a different cell type, # present in both human cancer and mouse immune cells. 38 P5 target proteins in LNCaP prostate cell line from Homo sapiens and 25 P5 target proteins from CD8+ immune cell from Mus musculus.Homo sapiens (Human)Carnitine palmitoyltransferase 1ADDX21Homo sapiens (Human)Nucleolar RNA helicase 2DHCR24aAlso known to interact with sterol in a different cell type, # present in both human cancer and mouse immune cells. 38 P5 target proteins in LNCaP prostate cell line from Homo sapiens and 25 P5 target proteins from CD8+ immune cell from Mus musculus.Homo sapiens (Human)Delta(24)-sterol reductaseDHX9Homo sapiens (Human)ATP-dependent RNA helicase AEMDaAlso known to interact with sterol in a different cell type, # present in both human cancer and mouse immune cells. 38 P5 target proteins in LNCaP prostate cell line from Homo sapiens and 25 P5 target proteins from CD8+ immune cell from Mus musculus.Homo sapiens (Human)EmerinGANABHomo sapiens (Human)Neutral alpha-glucosidase ABILF3Homo sapiens (Human)Interleukin enhancer-binding factor 3IMMTaAlso known to interact with sterol in a different cell type, # present in both human cancer and mouse immune cells. 38 P5 target proteins in LNCaP prostate cell line from Homo sapiens and 25 P5 target proteins from CD8+ immune cell from Mus musculus.Homo sapiens (Human)MICOS complex subunit MIC60LMNAaAlso known to interact with sterol in a different cell type, # present in both human cancer and mouse immune cells. 38 P5 target proteins in LNCaP prostate cell line from Homo sapiens and 25 P5 target proteins from CD8+ immune cell from Mus musculus.Homo sapiens (Human)Prelamin-A/CLMNB1Homo sapiens (Human)Lamin-B1MATR3Homo sapiens (Human)Matrin-3MYH9Homo sapiens (Human)Myosin-9NDC1Homo sapiens (Human)NucleoporinNDUFS1Homo sapiens (Human)NADH-ubiquinone oxidoreductaseNOP58Homo sapiens (Human)Nucleolar protein 58NPEPPS#Homo sapiens (Human)Puromycin-sensitive aminopeptidaseNUP93Homo sapiens (Human)Nuclear pore complex protein Nup93PARP1Homo sapiens (Human)Poly [ADP-ribose] polymerase 1PEBP1Homo sapiens (Human)Phosphatidylethanolamine-binding proteinPHBaAlso known to interact with sterol in a different cell type, # present in both human cancer and mouse immune cells. 38 P5 target proteins in LNCaP prostate cell line from Homo sapiens and 25 P5 target proteins from CD8+ immune cell from Mus musculus.Homo sapiens (Human)ProhibitinRPN1aAlso known to interact with sterol in a different cell type, # present in both human cancer and mouse immune cells. 38 P5 target proteins in LNCaP prostate cell line from Homo sapiens and 25 P5 target proteins from CD8+ immune cell from Mus musculus.Homo sapiens (Human)Dolichyl-diphosphooligosaccharide-protein glycosyltransferase subunit 1SURF4aAlso known to interact with sterol in a different cell type, # present in both human cancer and mouse immune cells. 38 P5 target proteins in LNCaP prostate cell line from Homo sapiens and 25 P5 target proteins from CD8+ immune cell from Mus musculus.Homo sapiens (Human)Surfeit 4TRAP1Homo sapiens (Human)Heat shock protein 75 kDa, mitochondrialUBA1Homo sapiens (Human)Ubiquitin-like modifier-activating enzyme 1XRCC6Homo sapiens (Human)X-ray repair complementing defective repair in Chinese hamster cells 6CPT2aAlso known to interact with sterol in a different cell type, # present in both human cancer and mouse immune cells. 38 P5 target proteins in LNCaP prostate cell line from Homo sapiens and 25 P5 target proteins from CD8+ immune cell from Mus musculus.Homo sapiens (Human)Carnitine O-palmitoyltransferase 2SF3B3Homo sapiens (Human)Splicing factor 3B subunit 3SFPQHomo sapiens (Human)Splicing factor, proline- and glutamine-richSRPRBaAlso known to interact with sterol in a different cell type, # present in both human cancer and mouse immune cells. 38 P5 target proteins in LNCaP prostate cell line from Homo sapiens and 25 P5 target proteins from CD8+ immune cell from Mus musculus.Homo sapiens (Human)Signal recognition particle receptor subunit betaTMX1Homo sapiens (Human)Thioredoxin-related transmembrane protein 1GLUD1Mus musculusGlutamate dehydrogenase 1P4HBMus musculusProlyl 4-hydroxylase, beta polypeptidePITRM1Mus musculusPitrilysin metallepetidase 1RAB11AaAlso known to interact with sterol in a different cell type, # present in both human cancer and mouse immune cells. 38 P5 target proteins in LNCaP prostate cell line from Homo sapiens and 25 P5 target proteins from CD8+ immune cell from Mus musculus.Mus musculusRAS oncogene familyCAMK2GMus musculusCalcium/calmodulin-dependent protein kinaseH2-D1aAlso known to interact with sterol in a different cell type, # present in both human cancer and mouse immune cells. 38 P5 target proteins in LNCaP prostate cell line from Homo sapiens and 25 P5 target proteins from CD8+ immune cell from Mus musculus.Mus musculusHistocompatibility 2, D region locus 1PGRMC2aAlso known to interact with sterol in a different cell type, # present in both human cancer and mouse immune cells. 38 P5 target proteins in LNCaP prostate cell line from Homo sapiens and 25 P5 target proteins from CD8+ immune cell from Mus musculus.Mus musculusP4 receptor membrane component 2VDAC1aAlso known to interact with sterol in a different cell type, # present in both human cancer and mouse immune cells. 38 P5 target proteins in LNCaP prostate cell line from Homo sapiens and 25 P5 target proteins from CD8+ immune cell from Mus musculus.Mus musculusVoltage-dependent anion channel 1VDAC2aAlso known to interact with sterol in a different cell type, # present in both human cancer and mouse immune cells. 38 P5 target proteins in LNCaP prostate cell line from Homo sapiens and 25 P5 target proteins from CD8+ immune cell from Mus musculus.Mus musculusVoltage-dependent anion channel 2VDAC3aAlso known to interact with sterol in a different cell type, # present in both human cancer and mouse immune cells. 38 P5 target proteins in LNCaP prostate cell line from Homo sapiens and 25 P5 target proteins from CD8+ immune cell from Mus musculus.Mus musculusVoltage-dependent anion channel 3DNAJC1aAlso known to interact with sterol in a different cell type, # present in both human cancer and mouse immune cells. 38 P5 target proteins in LNCaP prostate cell line from Homo sapiens and 25 P5 target proteins from CD8+ immune cell from Mus musculus.Mus musculusDnaJ heat shock protein familyATP13A1aAlso known to interact with sterol in a different cell type, # present in both human cancer and mouse immune cells. 38 P5 target proteins in LNCaP prostate cell line from Homo sapiens and 25 P5 target proteins from CD8+ immune cell from Mus musculus.Mus musculusATPase type 13A1CANXaAlso known to interact with sterol in a different cell type, # present in both human cancer and mouse immune cells. 38 P5 target proteins in LNCaP prostate cell line from Homo sapiens and 25 P5 target proteins from CD8+ immune cell from Mus musculus.Mus musculusCalnexinU2AFMus musculusU2 small nuclear ribonucleoprotein auxiliary factorECH1Mus musculusEnoyl coenzyme A hydratase 1VIMMus musculusVimentinPHB2Mus musculusProhibitin 2CLUHMus musculusClustered mitochondria (cluA/CLU1) homologNPEPPS#Mus musculusAminopeptidase puromycin sensitiveCYP51aAlso known to interact with sterol in a different cell type, # present in both human cancer and mouse immune cells. 38 P5 target proteins in LNCaP prostate cell line from Homo sapiens and 25 P5 target proteins from CD8+ immune cell from Mus musculus.Mus musculusCytochrome P450, family 51ANO10Mus musculusAnoctamin 10SLC25A20aAlso known to interact with sterol in a different cell type, # present in both human cancer and mouse immune cells. 38 P5 target proteins in LNCaP prostate cell line from Homo sapiens and 25 P5 target proteins from CD8+ immune cell from Mus musculus.Mus musculusMitochondrial carnitine/acylcarnitine translocase, memberZMPSTE24aAlso known to interact with sterol in a different cell type, # present in both human cancer and mouse immune cells. 38 P5 target proteins in LNCaP prostate cell line from Homo sapiens and 25 P5 target proteins from CD8+ immune cell from Mus musculus.Mus musculusZinc metallopeptidaseMTAPMus musculusMethylthioadenosine phosphorylaseLSSaAlso known to interact with sterol in a different cell type, # present in both human cancer and mouse immune cells. 38 P5 target proteins in LNCaP prostate cell line from Homo sapiens and 25 P5 target proteins from CD8+ immune cell from Mus musculus.Mus musculusLanosterol synthasea Also known to interact with sterol in a different cell type, # present in both human cancer and mouse immune cells. 38 P5 target proteins in LNCaP prostate cell line from Homo sapiens and 25 P5 target proteins from CD8+ immune cell from Mus musculus. Open table in a new tab P5-interactomes in LNCaP and CD8+ T cells were captured as per the schematics (Figures 3B and 3C). Hierarchical clustering showed the binding potential of the probes to be distinct, which might be associated with the availability of molecular space" @default.
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