Fig. 7.
CD47 regulation of autophagy. In the presence of cellular stress, blockade of CD47 activates gene expression of beclin-1 and autophagy related proteins (ATG) 5 and 7 that limit BCL-2 mediated pathways to induce cell death. The increase in beclin-1 ATG5 and ATG7 leads to increased autophagic flux by increasing expression of LC3 to form the autophagosome membrane and stimulates p62, which targets unwanted cargo to be degraded in the autophagosome. The radioprotective effect of CD47 is reversed by the administration of 3-methyladenine (3-MA), which inhibits early activation of autophagy, or the lysosomotropic agent hydroxychloroquine (HCQ), which inhibits autophagy at late stages of the pathway.
