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UCSC Genome Browser Gene Interaction Graph
Gene interactions and pathways from curated databases and text-mining
Cell 2009, PMID: 19303849

A role of DNA-PK for the metabolic gene regulation in response to insulin.

Wong, Roger H F; Chang, Inhwan; Hudak, Carolyn S S; Hyun, Suzanne; Kwan, Hiu-Yee; Sul, Hei Sook

Fatty acid synthase (FAS) is a central enzyme in lipogenesis and transcriptionally activated in response to feeding and insulin signaling. The transcription factor USF is required for the activation of FAS transcription, and we show here that USF phosphorylation by DNA-PK, which is dephosphorylated by PP1 in response to feeding, triggers a switch-like mechanism. Under fasting conditions, USF-1 is deacetylated by HDAC9, causing promoter inactivation. In contrast, feeding induces the recruitment of DNA-PK to USF-1 and its phosphorylation, which then allows recruitment of P/CAF, resulting in USF-1 acetylation and FAS promoter activation. DNA break/repair components associated with USF induce transient DNA breaks during FAS activation. In DNA-PK-deficient SCID mice, feeding-induced USF-1 phosphorylation/acetylation, DNA breaks, and FAS activation leading to lipogenesis are impaired, resulting in decreased triglyceride levels. Our study demonstrates that a kinase central to the DNA damage response mediates metabolic gene activation.

Document information provided by NCBI PubMed

Text Mining Data

Dashed line = No text mining data

Manually curated Databases

  • IRef Biogrid Interaction: USF1 — SREBF1 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: USF1 — KAT2B (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: TOP2B — USF1 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: USF1 — PRKDC (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: XRCC6 — USF1 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: USF1 — PARP1 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: USF1 — XRCC5 (physical association, affinity chromatography technology)
  • Gene Ontology Complexes transcription factor complex: transcription factor complex complex (ATF7IP-GSC-GCM1-MAFB-NKX2-1-NKX2-5-RARG-KLF4-FOXF1-FOXF2-FOXE3-LDB1-ZFHX3-GATA6-SNAI3-FOXH1-KAT5-AHR-EYA3-NFATC2-CRX-MED27-HES6-SKI-XRCC6-ARNTL-SUB1-JUN-SOX17-SCX-DMBX1-TCF4-TCF7-PDLIM1-TFEB-LBX1-TRRAP-NAA16-EPAS1-MGA-PTF1A-HOXD12-MEF2B-TFDP3-TFDP1-HDAC2-YY1-SMAD9-CLOCK-ONECUT3-SMAD5-SMAD6-SMAD7-SMAD1-SMAD2-PRKDC-RCOR2-NHLH2-REL-TBX5-ARNTL2-BSX-HOXA10-HOXB13-MED23-PUS1-TAL1-RBL1-RBL2-MINA-HMGA1-BARX2-LEF1-EP300-PMF1-ARID5A-WWTR1-LMO2-LMO4-TP73-ABT1-CDK2-DKFZp686M216-CREG1-CTNNB1-SOX9-HAND2-SOX2-TEAD2-MYOG-TEAD4-CEBPA-GFI1B-MYOD1-ALX1-NPAS4-TFAP2D-FIGLA-ALX4-ETS1-PROP1-ASCL3-HCLS1-MSX1-MSX2-SRA1-AJUBA-MTA2-SIN3A-POU3F2-POU3F1-BEX1-MLXIPL-NR2E3-PBX2-ANKRD1-E2F6-E2F5-E2F4-E2F3-E2F2-E2F1-E2F8-CREBBP-ATF5-ATF4-POU2F3)
  • IRef Hprd Interaction: Complex of 65 proteins
  • IRef Hprd Interaction: USF1 — PRKDC (in vitro)
  • IRef Hprd Interaction: USF1 — HDAC9 (in vivo)
  • IRef Intact Interaction: USF1 — KAT2B (acetylation reaction, acetylase assay)
  • IRef Intact Interaction: Complex of 11 proteins (association, anti tag coimmunoprecipitation)
  • IRef Intact Interaction: Complex of KAT2B-USF1-SREBF1 (association, anti bait coimmunoprecipitation)
  • IRef Intact Interaction: Complex of SREBF1-USF1-HDAC9 (association, anti bait coimmunoprecipitation)
  • IRef Intact Interaction: Complex of TOP2B-PRKDC-USF1-KAT2B-PARP1-XRCC5 (physical association, anti bait coimmunoprecipitation)
  • IRef Intact Interaction: Complex of TOP2B-HDAC9-PRKDC-XRCC5-USF1-PARP1-XRCC6-KAT2B-USF2 (association, anti bait coimmunoprecipitation)
  • IRef Intact Interaction: Complex of XRCC5-XRCC6-PRKDC-USF1 (phosphorylation reaction, protein kinase assay)
In total, 8055 gene pairs are associated to this article in curated databases