Fig. 4: New paradigm for the regulation of STAT2 protein in melanoma formation.
From: Stat2 stability regulation: an intersection between immunity and carcinogenesis
In normal cells, STAT2 protein levels are maintained at low levels. When cells are stimulated by UV, especially UVB, GSK3α/β phosphorylates STAT2 at the DBD, which recruits the SCFFBXW7 complex to form the SCFFBXW7–STAT2 complex. FBXW7 catalyzes K48 STAT2 polyubiquitination, resulting in a reduction in STAT2 protein levels via the proteasomal degradation pathway. Thus, cell proliferation at the acute stage is initially suppressed after UVB irradiation. However, in cancer cells with FBXW7 mutation(s), higher STAT2 protein levels are sustained compared to that of normal cells, resulting in the induction of cell proliferation.
