Fig. 5.

TRIM proteins regulate extrinsic and intrinsic apoptosis via diverse mechanisms. TRIMs regulate death receptor-mediated apoptosis by regulating the activation of initiator and executor CASPs and MAPK signaling cascades. TRIMs also regulate intrinsic apoptosis mediated by the mitochondria and the pro- and anti-apoptotic proteins BAX, BAK1, and BCL2. They induce the formation of mitochondrial pores to release CYCS, thereby inducing the formation of apoptosomes and the activation of CASP9 and CASP3. Some TRIMs activate anti-apoptotic BCL2 to inhibit mitochondrial pore formation and CYCS release, thereby preventing apoptosome formation and CASP9 activation. Several TRIM proteins are localized in the nucleus to regulate gene expression mediated by TP53, NFATs, and NFKB. NFKB; Nuclear factor kappa B, TGFB2; Transforming growth factor beta 2, FASLG; Fas ligand, TNF; Tumor necrosis factor, TGFBR2; Transforming growth factor beta receptor 2, FAS; Fas cell surface death receptor, TNFRSF1A; TNF receptor superfamily member 1A, PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha, DIAPH1; DIAPH1, APAF1; Apoptotic peptidase activating factor 1, DAXX; Death domain associated protein, NR4A1; Nuclear receptor subfamily 4 group A member 1, CASP8AP2; Caspase 8 associated protein 2, SUMO1; Small ubiquitin like modifier 1, FADD; Fas associated via death domain, CASP8; Caspase 8, CASP6; Caspase 6, CASP7; Caspase 7, CFLAR; CASP8 and FADD like apoptosis regulator, MAPK8; Mitogen-activated protein kinase 8, MAPK14; Mitogen-activated protein kinase 14, MAP2K3; Mitogen-activated protein kinase kinase 3, MAP3K5; Mitogen-activated protein kinase kinase kinase 5, TRADD; TNFRSF1A associated via death domain, RIPK1; Receptor interacting serine/threonine kinase 1, PMT1; Protein O-mannosyltransferase-1, AKT1; AKT serine/threonine kinase 1, MOAP1; Modulator of apoptosis 1, PEX5; Peroxisomal biogenesis factor 5, CASP9; Caspase 9, SIVA1; SIVA1 apoptosis inducing factor