Gene interactions and pathways from curated databases and text-mining
Science signaling 2009, PMID: 20029029

Regulation of epidermal growth factor receptor trafficking by lysine deacetylase HDAC6.

Deribe, Yonathan Lissanu; Wild, Philipp; Chandrashaker, Akhila; Curak, Jasna; Schmidt, Mirko H H; Kalaidzidis, Yannis; Milutinovic, Natasa; Kratchmarova, Irina; Buerkle, Lukas; Fetchko, Michael J; Schmidt, Philipp; Kittanakom, Saranya; Brown, Kevin R; Jurisica, Igor; Blagoev, Blagoy; Zerial, Marino; Stagljar, Igor; Dikic, Ivan

Binding of epidermal growth factor (EGF) to its receptor leads to receptor dimerization, assembly of protein complexes, and activation of signaling networks that control key cellular responses. Despite their fundamental role in cell biology, little is known about protein complexes associated with the EGF receptor (EGFR) before growth factor stimulation. We used a modified membrane yeast two-hybrid system together with bioinformatics to identify 87 candidate proteins interacting with the ligand-unoccupied EGFR. Among them was histone deacetylase 6 (HDAC6), a cytoplasmic lysine deacetylase, which we found negatively regulated EGFR endocytosis and degradation by controlling the acetylation status of alpha-tubulin and, subsequently, receptor trafficking along microtubules. A negative feedback loop consisting of EGFR-mediated phosphorylation of HDAC6 Tyr(570) resulted in reduced deacetylase activity and increased acetylation of alpha-tubulin. This study illustrates the complexity of the EGFR-associated interactome and identifies protein acetylation as a previously unknown regulator of receptor endocytosis and degradation.

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Text Mining Data

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Manually curated Databases

  • IRef Intact Interaction: PRCC — EGFR (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: EGFR — HSP90AA1 (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: EGFR — DYNC1H1 (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: CBR1 — EGFR (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: EGFR — TMCO3 (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: EEF1G — EGFR (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: EGFR — AKAP12 (physical association, anti tag coimmunoprecipitation)
  • IRef Intact Interaction: EGFR — AKAP12 (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: FKBP4 — EGFR (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: AHSA1 — EGFR (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: MEGF6 — EGFR (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: EGFR — DNAJC4 (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: EGFR — HDAC6 (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: EGFR — HDAC6 (phosphorylation reaction, protein kinase assay)
  • IRef Intact Interaction: EGFR — HDAC6 (physical association, anti tag coimmunoprecipitation)
  • IRef Intact Interaction: EGFR — HDAC6 (physical association, anti bait coimmunoprecipitation)
  • IRef Intact Interaction: PPP5C — EGFR (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: TPI1 — EGFR (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: EGFR — MAP3K12 (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: ARF6 — EGFR (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: CEND1 — EGFR (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: CSRP1 — EGFR (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: STIP1 — EGFR (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: STIP1 — EGFR (physical association, anti tag coimmunoprecipitation)
  • IRef Intact Interaction: PIN4 — EGFR (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: SEPP1 — EGFR (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: EGFR — RUSC2 (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: EGFR — OLFM1 (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: EGFR — FN1 (physical association, anti tag coimmunoprecipitation)
  • IRef Intact Interaction: EGFR — VAPA (physical association, anti tag coimmunoprecipitation)
  • IRef Intact Interaction: EGFR — VAPA (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: ALDOA — EGFR (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: GPM6B — EGFR (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: FKBP8 — EGFR (physical association, anti tag coimmunoprecipitation)
  • IRef Intact Interaction: FKBP8 — EGFR (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: FKBP8 — EGFR (physical association, anti bait coimmunoprecipitation)
  • IRef Intact Interaction: RAP1GDS1 — EGFR (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: DCTN2 — EGFR (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: EGFR — GSN (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: SNAP25 — EGFR (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: EGFR — ARPC5 (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: TXN — EGFR (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: EGF — HDAC6 (colocalization, confocal microscopy)
  • IRef Intact Interaction: YWHAQ — EGFR (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: YWHAQ — EGFR (physical association, anti bait coimmunoprecipitation)
  • IRef Intact Interaction: YWHAQ — EGFR (physical association, anti tag coimmunoprecipitation)
  • IRef Intact Interaction: SH3D21 — EGFR (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: PDK3 — EGFR (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: EGFR — HSP90AB1 (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: KCTD9 — EGFR (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: SYN1 — EGFR (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: PLCH1 — EGFR (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: Complex of AIP-AIP-EGFR-EGFR (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: Complex of HSPA1A-HDAC6-AP2A1-EGFR-MAP3K12 (association, anti bait coimmunoprecipitation)
  • IRef Intact Interaction: PNPLA2 — EGFR (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: EGFR — HSPA9 (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: CNTN2 — EGFR (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: EGFR — UBE2V2 (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: EGFR — CFL1 (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: EGFR — SH3BGRL3 (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: HSPA4 — EGFR (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: PTPN12 — EGFR (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: EGFR — STUB1 (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: EGFR — OAZ1 (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: GOT1 — EGFR (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: GAPDH — EGFR (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: GAPDH — EGFR (physical association, anti tag coimmunoprecipitation)
  • IRef Intact Interaction: HSPA1A — EGFR (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: HSPA1A — EGFR (physical association, anti tag coimmunoprecipitation)
  • IRef Intact Interaction: NDN — EGFR (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: EGFR — HEXIM1 (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: ERBB4 — HDAC6 (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: EGFR — GABARAPL2 (physical association, pull down)
  • IRef Intact Interaction: EGFR — GABARAPL2 (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: MGARP — EGFR (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: EGFR — PRKAR1B (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: EGFR — RAB3A (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: ATIC — EGFR (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: COL9A3 — EGFR (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: SH3BGRL — EGFR (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: ERBB3 — HDAC6 (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: MAST1 — EGFR (physical association, anti tag coimmunoprecipitation)
  • IRef Intact Interaction: MAST1 — EGFR (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: EGFR — AHNAK (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: SORBS2 — EGFR (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: EGFR — HSP90B1 (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: PRDX1 — EGFR (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: EGFR — UROD (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: PSMD4 — EGFR (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: SPCS2 — EGFR (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: EGFR — MOB4 (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: MATR3 — EGFR (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: EGFR — CALM1 (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: ANXA1 — EGFR (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: ADRM1 — EGFR (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: EGFR — PTGDS (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: FAH — EGFR (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: UCHL1 — EGFR (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: UCHL1 — EGFR (physical association, anti tag coimmunoprecipitation)
  • IRef Intact Interaction: PSMA7 — EGFR (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: AP2M1 — EGFR (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: ERBB2 — HDAC6 (physical association, ubiquitin reconstruction)
  • IRef Intact Interaction: MDH1 — EGFR (physical association, ubiquitin reconstruction)
In total, 94 gene pairs are associated to this article in curated databases