{"database":"GEO","file_versions":[],"scores":null,"additional":{"omics_type":["Genomics"],"species":["Homo sapiens"],"gds_type":["Genome binding/occupancy profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE330345"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Photoproximity labeling of c-Myc reveals SLK as a cancer-specific co-regulator [ChIP-Seq]","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, yet underexplored, alternative approach. Here we report a strategy for capturing cancer-specific protein-protein interactions using context-dependent µMap photoproximity labeling. Using an intein-based method for catalyst conjugation in biochemically intact nuclei, we demonstrate that we can capture unique protein interactomes of c-Myc in healthy and cancerous prostate cell lines, and that these unique interactors can be mined to identify druggable vulnerabilities. We find that a cancer-specific c-Myc interactor, STE20 like kinase (SLK), selectively promotes c-Myc stabilization at the protein level, drives epithelial morphology, and is essential for tumorigenesis, validating it as a viable therapeutic target. Mechanistically, this stabilization is driven by SLK-mediated phosphorylation of c-Myc at serine 329, which antagonizes GSK3β-dependent phosphorylation of the c-Myc phosphodegron and effectively increases the stability of c-Myc. This cancer-selective interaction is enabled by a change in SLK splicing that promotes nuclear localization of the long isoform, rather than changes at the protein or total RNA level. Furthermore, analysis of cancer patient data shows a strong correlation between the SLK long splice isoform and expression of c-Myc targets across multiple tumor types. Importantly, the SLK-c-Myc interaction is validated in cancer cell lines from diverse tissues, suggesting this novel regulatory axis is broadly operative across human cancer.","dates":{"publication":"2026/05/17"},"accession":"GSE330345","cross_references":{"GSM":["GSM9724229","GSM9724239","GSM9724228","GSM9724238","GSM9724227","GSM9724226","GSM9724237","GSM9724236","GSM9724235","GSM9724245","GSM9724234","GSM9724244","GSM9724233","GSM9724232","GSM9724243","GSM9724242","GSM9724231","GSM9724241","GSM9724230","GSM9724240"],"GPL":["18573"],"GSE":["330345"],"taxon":["Homo sapiens"]}}