Gene interactions and pathways from curated databases and text-mining
Nature 2008, PMID: 18235501

DBC1 is a negative regulator of SIRT1.

Kim, Ja-Eun; Chen, Junjie; Lou, Zhenkun

The NAD-dependent protein deacetylase Sir2 (silent information regulator 2) regulates lifespan in several organisms. SIRT1, the mammalian orthologue of yeast Sir2, participates in various cellular functions and possibly tumorigenesis. Whereas the cellular functions of SIRT1 have been extensively investigated, less is known about the regulation of SIRT1 activity. Here we show that Deleted in Breast Cancer-1 (DBC1), initially cloned from a region (8p21) homozygously deleted in breast cancers, forms a stable complex with SIRT1. DBC1 directly interacts with SIRT1 and inhibits SIRT1 activity in vitro and in vivo. Downregulation of DBC1 expression potentiates SIRT1-dependent inhibition of apoptosis induced by genotoxic stress. Our results shed new light on the regulation of SIRT1 and have important implications in understanding the molecular mechanism of ageing and cancer.

Document information provided by NCBI PubMed

Text Mining Data

SIRT1 ⊣ DBC1: " DBC1 directly interacts with SIRT1 and inhibits SIRT1 activity in vitro and in vivo "

Manually curated Databases

  • IRef Biogrid Interaction: NOC4L — SIRT1 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: CHD3 — SIRT1 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: TAF2 — SIRT1 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: RAP1A — SIRT1 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: SART1 — SIRT1 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: SIRT1 — TP53 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: SIRT1 — TP53 (direct interaction, enzymatic study)
  • IRef Biogrid Interaction: BRINP1 — SIRT1 (physical association, affinity chromatography technology)
  • IRef Dip Interaction: CCAR2 — SIRT1 (direct interaction, pull down)
  • IRef Dip Interaction: CCAR2 — SIRT1 (direct interaction, anti bait coimmunoprecipitation)
  • IRef Dip Interaction: CCAR2 — SIRT1 (direct interaction, anti tag coimmunoprecipitation)
  • IRef Dip Interaction: CCAR2 — TP53 (physical association, anti tag coimmunoprecipitation)
  • IRef Dip Interaction: Complex of NOC4L-TRIM28-CHD3-CCAR2-SIRT1-SART1 (physical association, pull down)
  • IRef Dip Interaction: SIRT1 — FOXO1 (physical association, anti tag coimmunoprecipitation)
  • IRef Dip Interaction: TP53 — SIRT1 (direct interaction, deacetylase assay)
  • IRef Dip Interaction: TP53 — SIRT1 (direct interaction, anti tag coimmunoprecipitation)
  • IRef Intact Interaction: Complex of SART1-CHD3-NOC4L-SIRT1-CCAR2 (association, pull down)
  • IRef Intact Interaction: CCAR2 — SIRT1 (physical association, anti bait coimmunoprecipitation)
  • IRef Intact Interaction: CCAR2 — SIRT1 (physical association, pull down)
  • IRef Intact Interaction: CCAR2 — SIRT1 (physical association, anti tag coimmunoprecipitation)
  • IRef Intact Interaction: TP53 — SIRT1 (deacetylation reaction, deacetylase assay)
  • Reactome Reaction: SIRT1 → CCAR2 (reaction)
  • Reactome Reaction: SIRT1 → CCAR2 (direct_complex)
In total, 21 gene pairs are associated to this article in curated databases