SERPINB3 enhances NPM1 sumoylation via inhibiting SENP3's activity and promotes lung tumorigenesis.

ABSTRACT: SERPINB3 or SCCA1, a member of the serine proteinase inhibitor family, is frequently overexpressed in multiple malignancies, including lung adenocarcinoma (LUAD). However, its molecular mechanisms and endogenous substrates in lung cancer remain poorly characterized. Here, we identified SUMO-specific proteinase 3 (SENP3) as a novel direct interaction partner and functional target of SERPINB3 in LUAD. Using proximity-dependent biotin labeling coupled with mass spectrometry, we discovered that SERPINB3 forms a nuclear complex with SENP3 and nucleophosmin (NPM1). This tripartite interaction was validated through endogenous co-immunoprecipitation and bimolecular fluorescence complementation assays. Structural modeling with AlphaFold3 and subsequent mutagenesis studies revealed that SERPINB3 bin

SUBMITTER: Meng X 

PROVIDER: S-EPMC12847774 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature