Identification and characterization of a TGF-β-independent SMAD4-NFATc1-STAT3 regulatory axis.

ABSTRACT: SMAD4, a central mediator of the TGF-β signaling pathway, plays a critical role in regulating cellular processes such as proliferation, differentiation, and apoptosis. While SMAD4's canonical functions within TGF-β signaling are well-established, its non-canonical, TGF-β-independent roles remain poorly understood, particularly in the context of disease biology. Here, we investigate SMAD4's TGF-β-independent functions by identifying and characterizing its protein-protein interaction network. Using pancreatic ductal adenocarcinoma as a model system, we performed a SMAD4-focused oncogenic protein-protein interaction mapping and uncovered a novel interaction between SMAD4 and NFATc1. We demonstrated that SMAD4 binds to NFATc1 in a phosphorylation-dependent but TGF-β-independent manner, sequest

SUBMITTER: Ouyang W 

PROVIDER: S-EPMC12831459 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature