Fig. 2.

RING domain-containing TRIMs act as E3-Ub ligase and conjugate Ub to the target substrate, regulating autophagy. a Three enzymes catalyze the transfer of Ub to the target substrate. E1 catalyzes the conversion of Ub to E2 via ATP hydrolysis. E3-Ub ligases containing RING domains directly transfer Ub to the target substrate, whereas HECT and RBR E3-Ub ligases form E3-Ub intermediates before transferring Ub to the target substrates. b Various signal inputs converge on the main autophagy regulator MTOR, such as PIK3CA, TP53, MAPK3/MAPK1, hunger, and PRKAA2/AMPK. Activation of the MTOR kinase complex inhibits autophagy by inducing inhibitory phosphorylation of the autophagy-initiating kinase ULK1. PRKAA2 activated autophagy by phosphorylating ULK1. TRIM proteins regulate various steps of canonical autophagy, including autophagy initiation, phagophore formation, MAP1LC3 conjugation, and efficient targeting of substrates to autophagosomes via autophagy receptors and Ub. Autophagosomes fuse with lysosomes to form autolysosomes, which degrade the entrapped cargo materials. TRIM; Tripartite motif containing, Ub; Ubiquitin, ATP; Adenosine triphosphate, RING; Really interesting new gene, HECT; Homologous to the E6-AP carboxyl terminus, RBR; RING-in-between-RING, MTOR; Mechanistic target of rapamycin kinase, PIK3CA; Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha, TP53; Tumor protein 53, MAPK3/MAPK1; mitogen-activated protein kinase 3/1, PRKAA2/AMPK; Protein kinase AMP-activated catalytic subunit alpha 2, ULK1; Unc-51 like autophagy activating kinase 1, MAP1LC3B2; Microtubule associated protein 1 light chain 3 beta 2, AKT1; AKT serine/threonine kinase 1, PPi; Inorganic pyrophosphate, AMP; Adenosine monophosphate, RUBCN; rubicon autophagy regulator, BCL2; BCL2 apoptosis regulator, ATG13; Autophagy related 13, RB1CC1; RB1 inducible coiled-coil 1, ATG10; Autophagy related 10, ATG7; Autophagy related 7, ATG12; Autophagy related 12, ATG14; Autophagy related 14, PIK3C3; Phosphatidylinositol 3-kinase catalytic subunit type 3, PIK3R4; phosphoinositide-3-kinase regulatory subunit 4, BECN1; Beclin 1, ATG16L1; Autophagy related 16 like 1, ATG5; Autophagy related 5, AR; Autophagy receptor, CALCOCO2; Calcium binding and coiled-coil domain 2, NBR1; NBR1 autophagy cargo receptor, SQSTM1; Sequestome 1, TAX1BP1; Tax1 binding protein 1, OPTN; Optineurin, TRIM16; Tripartite motif containing 16, ATG10; Autophagy related 10, ATG7; Autophagy related 7, ATG12; Autophagy related 12, ATG13; Autophagy related 13, DUB; Deubiquitinase