Figure 4.

Possible mechanisms underlying the differential regulation of protein (and in particular, VISTA) expression by the TGF-β-Smad3 pathway. (A) Changes in cell surface-based TGFBR levels. An example where galectin-9 expression is upregulated, and VISTA is downregulated is shown. The key message of this scheme is that the expression of target proteins could be differentially regulated by the TGF-β-Smad3 pathway, recruiting Smad4/TRIM33 co-activators. Differential responses are possibly determined by alterations of TGFBR levels on the surface of target cells. In the second scenario, “a” and “b” represent numbers of respective protein molecules. (B) Possibility of activation of a hypothetical protein-repressor of VSIG is depicted; (C) TGF-β-triggered changes in the localization of VSIG-containing locus during nuclear compartmentalisation in cell types where VISTA is downregulated by TGF-β (most likely scenario).