Figure 8.

Proposed model for the role of DAPK1‐mediated Beclin‐1 phosphorylation and TTP‐mediated Bcl‐2 mRNA destabilization in autophagy leading to the suppression of inflammatory responses by gAcrp in macrophages. Bcl‐2 protein binds to Beclin‐1 through its BH3 domain. The activation of DAPK1 by gAcrp facilitates Beclin‐1 phosphorylation at Thr¹¹⁹ and inhibits binding to its inhibitory protein Bcl‐2, which leads to autophagosome formation. For the other way, the level of Bcl‐2 protein itself is reduced by gAcrp through TTP‐mediated mRNA instability. AMPKα1/FoxO3A axis signalling acts as an upstream pathway that leads to the induction of TTP protein. The Adipo1 receptor (AdipoR1), rather than the Adipo2 receptor, plays a predominant role in the modulation of DAPK/Beclin‐1 signalling and AMPK/FoxO3A/TTP/Bcl2 axis by gAcrp in macrophages. Both DAPK1 activation and TTP induction are involved in autophagy activation via the modulation of Beclin‐1 and Bcl‐2 protein interaction, which inhibits LPS‐primed inflammatory cytokines expression