Nanoscale photoproximity labeling of c-Myc predicts cancer specific therapeutic targets
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1327355 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Transcription factors (TFs) have long been aspirational therapeutic targets for the treatment of diseases, as their dysregulation is a common mechanism for altered cell states. Despite this, many TFs implicated in disease have disordered structures and lack canonical binding pockets, rendering them non-trivial targets for small molecule-based therapies. Directly inhibiting TF function has proven difficult, but indirect inhibition by targeting the effector molecules that modulate TF function is a promising alternative strategy. Here we report a unified strategy for capturing cancer-specific protein-protein interactions using µMap photoproximity labeling. Using a recently reported intein-based strategy for catalyst conjugation in biochemically intact nuclei, we demonstrate that we can capture unique protein interactomes of c-Myc in androgen receptor dependent and independent prostate cancer cell lines, and that these unique interactors can be mined to identify druggable vulnerabilities. We find that a PC-3 specific Myc interactor, SLK, selectively promotes Myc stabilization and drives epithelial morphology only in androgen receptor negative prostate cancer.
2025-09-16 | GSE307813 | GEO
Project description:Tracking chromatin state changes using nanoscale protoproximity labeling
| PRJNA915358 | ENA
Project description:Tracking chromatin state changes using nanoscale protoproximity labeling (ATAC-Seq)
| PRJNA915471 | ENA
Project description:Tracking chromatin state changes using nanoscale protoproximity labeling (RNA-Seq)
| PRJNA915472 | ENA
Project description:Nanoscale Acoustic Oscillator for Mechanoimmunology: NAOMI
| PRJNA1294740 | ENA
Project description:Mechanoimmunology provides a powerful framework for understanding how mechanical forces orchestrate immune responses, offering insights into immune cell functions and the mechanisms underlying mechanotransduction. However, a major challenge in this field is the absence of reliable platforms that deliver precise and consistent mechanical stimuli to individual cells while achieving practical and reproducible mechanobiological activation of immune cells. In this work, we introduce a highly sensitive and stable nanoscale acoustic oscillator for mechanoimmunology applications: NAOMI. NAOMI features a micropatterned substrate that promotes uniform cell monolayer formation, seamlessly integrated with an acoustic transducer system capable of generating precise nanoscale oscillations (±1 nm deviation) for up to 72 h of continuous stimulation. Unlike conventional passive mechanobiological platforms that rely on static stiffness or topographical cues, NAOMI enables programmable, uniform 3D oscillations, delivering finely tuned and reproducible mechanical stimulation for diverse experimental applications. Validation studies demonstrate that NAOMI-induced oscillations significantly amplify stress intensity and cell displacement, driving robust M1 pro-inflammatory polarization in macrophages. With its high precision, stability, and tunability, NAOMI offers a powerful and versatile platform for studying mechanoimmunology and holds strong potential to support future research and enable innovative immunotherapy applications.
2025-08-20 | GSE303278 | GEO
Project description:Proximity-based biotin labeling assay in HEK293 cells using FlagBirA-Myc (WT and mutants) fusion proteins.
2017-11-20 | MSV000081725 | MassIVE
Project description:Systemic metabolic alterations associated with increased consumption of saturated fat and obesity are linked with increased risk of prostate cancer progression and mortality, but the molecular underpinnings of this association are poorly understood. Here, we demonstrate in a murine prostate cancer model, that high-fat diet (HFD) enhances the MYC transcriptional program through metabolic alterations that favour histone H4K20 hypomethylation at the promoter regions of MYC regulated genes, leading to increased cellular proliferation and tumour burden. Saturated fat intake (SFI) is also associated with an enhanced MYC transcriptional signature in prostate cancer patients. The SFI-induced MYC signature independently predicts prostate cancer progression and death. Finally, switching from a high-fat to a low-fat diet, attenuates the MYC transcriptional program in mice. Our findings suggest that in primary prostate cancer, dietary SFI contributes to tumour progression by mimicking MYC over expression, setting the stage for therapeutic approaches involving changes to the diet.
2019-08-22 | MTBLS135 | MetaboLights
Project description:Multiple myeloma (MM) is a malignant plasma cell disorder and frequently characterized by the 16 dysregulation of the MYC oncogene, which is associated with poor prognosis and disease progression. While MYC's involvement in transcriptional regulation is well-established, the functional role of MYC target proteins and the impact on post-transcriptional processes in MM cells remain poorly understood. This study employed Stable Isotope Labeling with Amino Acids in Cell Culture (SILAC) coupled with mass spectrometry analysis to investigate the effects of MYC depletion on the proteome of MM cells. The results revealed that MYC primarily regulates translational processes. Specifically, the three RNA-binding proteins (RBPs) 4EBP1, hnRNPC, and LARP1, were prominently down-regulated upon MYC depletion in MM cells. Notably, high expression levels of these proteins were correlated with poor survival and disease progression in MM patients. These findings highlight the critical role of MYC in the regulation of translation and identify 4EBP1, hnRNPC, and LARP1 as MYC target proteins. Targeting these proteins may offer new therapeutic strategies and prognostic markers for MM, potentially improving patient outcomes. This study provides valuable insights into the post-transcriptional regulatory mechanisms mediated by MYC and opens avenues for further research in understanding and treating this devastating disease.
2023-06-15 | MSV000092169 | MassIVE
Project description:Proximity labeling traditionally identifies interactomes of a single protein or RNA, though this approach limits mechanistic understanding of biomolecules functioning within complex systems. Here, we demonstrate a strategy for deciphering ligand-induced changes to global biomolecular interactions by enabling proximity labelling at the mesoscale, across an entire cellular system. By inserting nanoscale proximity labelling catalysts throughout chromatin, this system, MesoMap, provided new insights into how HDAC inhibitors regulate gene expression. Furthermore, it revealed that the orphaned drug candidate, SR-1815, regulates disease-linked Syngap1 gene expression through direct inhibition of kinases implicated in both neurological disorders and cancer. Through precise mapping of global chromatin mobility, MesoMap promotes insights into how drug-like chemical probes induce transcriptional dynamics within healthy and disease-associated cellular states.
2025-08-08 | GSE304410 | GEO