Fig. 6

Phosphorylation-mediated deubiquitination and stabilization of ACE2 protein. A ACE2 Ser680 phosphorylation by AMPK reduces MDM2-mediated ACE2 Lys788 ubiquitination, resulting in ACE2 protein stabilization. B ACE2 Ser776 and Ser783 phosphorylation by GLK (MAP4K3) reduces UBR4-mediated ACE2 Lys26, Lys112, and Lys114 ubiquitination, resulting in enhancement of ACE2 stabilization. C CK1α phosphorylates ACE2 in the ³SSS⁵ region, inducing the interaction between ACE2 and SPOP. Binding of SPOP prevents ACE2 ubiquitination from other E3 ligase(s), leading to protection of ACE2 protein from proteasomal degradation. aD The induction of surface ACE protein levels may be mediated by phosphorylation of the kinase NUAK2 at unidentified ACE2 residues. Red arrows denote enhancement of ACE2 stability; blue arrows denote ACE2 downregulation through proteasomal degradation