GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE345nnn/GSE345051/primaryOK200OtherHomo sapiensOtherhttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE345051GEOGSEfalseDIPTAR: A synthetic biology platform for functional interrogation of protein degradationProtein degradation regulates cellular homeostasis, yet many degradation events are difficult to study because they lack a readily selectable phenotype. Here, we develop Degradation-Induced Pyroptosis TArgeting Receptors (DIPTAR), a modular synthetic biology platform that couples protein degradation to CARD8-mediated pyroptosis. Using HIF-1α as a model substrate, we show that DIPTAR faithfully reports oxygen-dependent VHL-mediated degradation and enables pooled CRISPR screening to identify established and previously unrecognized regulators of HIF-1α stability. DIPTAR is functional across multiple cell types and can be programmed with diverse proteins, including BRD4, IκBα, and p53, to convert distinct degradation stimuli into a common pyroptotic output. DIPTAR also detects pathogen-mediated perturbations of host degradation pathways, including both inhibition and induction of degradation-dependent signaling. By converting protein degradation into a robust selectable phenotype, DIPTAR provides a scalable platform for functional genetic discovery, interrogation of degradation pathways, degrader characterization, and investigation of host-pathogen interactions.2026/08/26GSE345051GSM9992599GSM9992598GSM9992597GSM9992596GSM9992600GSM9992595GSM999259430173345051Homo sapiens