Fig. 8 | Signal Transduction and Targeted Therapy

Fig. 8

From: Epigenetic and post-translational modifications in autophagy: biological functions and therapeutic targets

Fig. 8

Crosstalk between phosphorylation and ubiquitination in autophagy regulation. SMURF1 forms a complex with UVRAG by binding to the PPxf motif and catalyzes K29- and K33-linked polyubiquitination of UVRAG at the K517 and K599 residues. Ubiquitinated UVRAG blocks RUBCN’s approach to the UVRAG-containing PIK3C3 complex, inhibiting the negative effect of RUBCN and promoting autophagosome maturation. CSNK1A1-mediated UVRAG phosphorylation at S522 disrupts the binding of SMURF1 to UVRAG and reverses UVRAG ubiquitination-mediated autophagosome maturation. CaMKII phosphorylates Beclin1 at S90 and subsequently increases TRAF6-catalyzed Beclin1 K63-ubiquitination, collectively contributing to autophagy induction for K63-linked ubiquitylated Id-1/2 degradation

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