Transforming growth factor-β3 regulates cell junction restructuring via MAPK-mediated mRNA destabilization and Smad-dependent protein degradation of Junctional adhesion molecule B (JAM-B).

This study aims to investigate the effects of TGF-β3 on the expression of JAM-B as well as the underlying mechanisms on how TGF-β3 regulates JAM-B expression to facilitate the disassembly of the BTB and apical ES. Our results revealed that TGF-β3 suppresses JAM-B at post-transcriptional and post-translational levels. Inhibitor, siRNA knockdown and co-immunoprecipitation have shown that TGF-β3 induces JAM-B protein degradation via ubiquitin-proteasome pathway. Immunofluorescence staining further confirmed that blockage of ubiquitin-proteasome pathway could abrogate TGF-β3-induced loss of JAM-B at the cell-cell interface. siRNA knockdown and immunofluorescence staining also demonstrated that activation of Smad signaling is required for TGF-β3-induced JAM-B protein degradation. In addition, TGF-β3 reduces JAM-B mRNA levels, at least in part, via post-transcriptional regulation. mRNA stability assay has confirmed that TGF-β3 promotes the degradation of JAM-B transcript and TGF-β3-mediated mRNA destabilization requires the activation of ERK1/2 and p54 JNK signal cascades. Taken together, TGF-β3 significantly downregulates JAM-B expression via post-transcriptional and post-translational modulation and results in the disruption of BTB and apical ES.
PMID: 25817991 [PubMed - as supplied by publisher]

Source: Biochimica et Biophysica Acta - March 25, 2015 Category: Biochemistry Authors: Zhang X, Lui WY Tags: Biochim Biophys Acta Source Type: research