Acetylation-ubiquitination crosstalk in NLRP3-gasdermin pyroptosis: a substrate-state framework with relevance to ulcerative colitis.

Acetylation and ubiquitination regulate inflammatory cell death, but evidence that they act together in ulcerative colitis (UC) remains limited. This review examines their interactions in nucleotide-binding oligomerisation domain-, leucine-rich repeat- and pyrin domain-containing protein 3 (NLRP3) and gasdermin D (GSDMD), drawing on a targeted PubMed search for literature published through 10 August 2026. We distinguish coupling tested within one study from separate mechanisms affecting the same substrate, and report human, intestinal and non-intestinal evidence separately. Studies of phosphoglycerate dehydrogenase, the glucocorticoid-induced tumour necrosis factor receptor and histone deacetylase 4 support acetylation-ubiquitination coupling in non-intestinal systems. These findings differ in site resolution and do not establish competition between the modifications at one lysine. Other studies show that acetylation affects NLRP3 assembly or GSDMD activity, while ubiquitination regulates substrate abundance, assembly and degradation. In experimental colitis, selected NLRP3 ubiquitin pathways and GSDMD acetylation mechanisms influence inflammation, but the complete coupled pathways have not been demonstrated in human UC. We organise these findings around four substrate properties: abundance, activation competence, localisation and persistence. This framework is a descriptive synthesis, not a validated evidence hierarchy or clinical biomarker. Its relevance to UC depends on establishing modification coupling in defined intestinal cell types and distinguishing that coupling from broader anti-inflammatory or barrier-protective effects.