Review Article

Role of Transcription Factor Modifications in the Pathogenesis of Insulin Resistance

Figure 2

Post-translational modifications (PTMs) of transcription factors. (a) The positions of PTM sites in the human FOXO1, SREBP-1c, and NF-κB p65 subunit.The positions of PTM sites and the implicated modifying enzymes are shown. and (–) represent activation and inhibition of the transcriptional activity of transcription factors, respectively. L1-2, nuclear localization sequences; E1-3, nuclear export sequences; DBD, DNA-binding domain; TAD, transactivation domain; RHD, Rel homology domain; NLS, nuclear localization sequence; TAD, transactivation domain. (b) Regulation of FOXO1 nucleocytoplasmic shuttling and transcriptional activity by PTMs in liver. (c) Regulation of transcription factor activities by PTMs in pancreatic β cells. P, phosphate group; Ac, acetyl group; G, O-linked-N-acetylglucosamine; Ub, ubiquitin; S, SUMO; Akt, v-akt murine thymoma viral oncogene homolog 1 (also known as protein kinase B [PKB]); SGK, serum/glucocorticoid-regulated kinase; CK1, casein kinase 1; DYRK1A, dual-specificity tyrosine-phosphorylated and regulated kinase1 A; CDK2, cyclin-dependent kinase 2. PI3K, phosphoinositide-3-kinase; PDK, phosphatidylinositol-dependent protein kinase; OGT, O-linked N-acetylglucosamine (GlcNAc) transferase; MAPK1/3, mitogen-activated protein kinase 1/3; Ubc9, ubiquitin conjugating enzyme 9; p300, E1A-binding protein p300; CBP, CREB-binding protein; SIRT1, sirtuin 1; PKA, protein kinase A; cAMP, cyclic adenosine monophosphate; SIK, salt-inducible kinase; GSK-3, glycogen synthase kinase-3; JNK, c-Jun N-terminal kinase; PCAF, CBP/p300-associated factor; MSK1, mitogen/stress-activated protein kinase 1; PKCζ, protein kinase Cζ; IKK, I kappa B kinase; CK2, casein kinase 2; TBK1, tank-binding kinase 1; SOCS-1, suppressor of cytokine signaling 1; HBP, hexosamine biosynthesis pathway; OGA, O-GlcNAcase; PDX1, pancreatic and duodenal homeobox 1; NeuroD, neurogenic differentiation; MafA, v-maf (maf musculoaponeurotic fibrosarcoma) oncogene homolog A.
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