biostudies-literatureKelebeev JYork UniversityHeart and Stroke Foundation of CanadaInstitute of Musculoskeletal Health and ArthritisCIHRjcs263527https://www.ebi.ac.uk/biostudies/studies/S-EPMC11928053biostudies-literatureUnknown138(4)Characterization of protein-protein interactions (PPIs) is a fundamental goal in the post-genomic era. Here, we document a generally applicable approach to identify cellular protein interactomes using a combination of nanobody-based affinity purification (AP) coupled with liquid chromatography and tandem mass spectrometry (LC-MS/MS). The Hippo signaling regulator TAZ (also known as WWTR1) functions as a transcriptional co-repressor or activator depending on its PPI network; we therefore undertook an unbiased proteomic screen to identify TAZ PPIs in striated muscle cells. A GFP nanotrap-based AP approach coupled with protein identification through LC-MS/MS was used to document a comprehensive list of known and novel TAZ interactome components. Informatic analysis of the interactome documentJournal of cell scienceTAZ interactome analysis using nanotrap-based affinity purification-mass spectrometry.PMC11928053PJT-159644PJT 159644MacKeracher AKelebeev JMcDermott JCMiyake TfalseTAZ interactome analysis using nanotrap-based affinity purification-mass spectrometry.Characterization of protein-protein interactions (PPIs) is a fundamental goal in the post-genomic era. Here, we document a generally applicable approach to identify cellular protein interactomes using a combination of nanobody-based affinity purification (AP) coupled with liquid chromatography and tandem mass spectrometry (LC-MS/MS). The Hippo signaling regulator TAZ (also known as WWTR1) functions as a transcriptional co-repressor or activator depending on its PPI network; we therefore undertook an unbiased proteomic screen to identify TAZ PPIs in striated muscle cells. A GFP nanotrap-based AP approach coupled with protein identification through LC-MS/MS was used to document a comprehensive list of known and novel TAZ interactome components. Informatic analysis of the interactome document2025-01-01T00:00:00Z2025 Feb2026-06-01T14:42:25.364Z2026-04-08T13:21:55.592ZS-EPMC119280533989843910.1242/jcs.263527