Gene interactions and pathways from curated databases and text-mining
Genes Dev 1999, PMID: 9990852

The SCFbeta-TRCP-ubiquitin ligase complex associates specifically with phosphorylated destruction motifs in IkappaBalpha and beta-catenin and stimulates IkappaBalpha ubiquitination in vitro.

Winston, J T; Strack, P; Beer-Romero, P; Chu, C Y; Elledge, S J; Harper, J W

Ubiquitin-mediated proteolysis has a central role in controlling the intracellular levels of several important regulatory molecules such as cyclins, CKIs, p53, and IkappaBalpha. Many diverse proinflammatory signals lead to the specific phosphorylation and subsequent ubiquitin-mediated destruction of the NF-kappaB inhibitor protein IkappaBalpha. Substrate specificity in ubiquitination reactions is, in large part, mediated by the specific association of the E3-ubiquitin ligases with their substrates. One class of E3 ligases is defined by the recently described SCF complexes, the archetype of which was first described in budding yeast and contains Skp1, Cdc53, and the F-box protein Cdc4. These complexes recognize their substrates through modular F-box proteins in a phosphorylation-dependent manner. Here we describe a biochemical dissection of a novel mammalian SCF complex, SCFbeta-TRCP, that specifically recognizes a 19-amino-acid destruction motif in IkappaBalpha (residues 21-41) in a phosphorylation-dependent manner. This SCF complex also recognizes a conserved destruction motif in beta-catenin, a protein with levels also regulated by phosphorylation-dependent ubiquitination. Endogenous IkappaBalpha-ubiquitin ligase activity cofractionates with SCFbeta-TRCP. Furthermore, recombinant SCFbeta-TRCP assembled in mammalian cells contains phospho-IkappaBalpha-specific ubiquitin ligase activity. Our results suggest that an SCFbeta-TRCP complex functions in multiple transcriptional programs by activating the NF-kappaB pathway and inhibiting the beta-catenin pathway.

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Text Mining Data

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Manually curated Databases

  • IRef Biogrid Interaction: NFKBIA — BTRC (direct interaction, unspecified method)
  • IRef Biogrid Interaction: NFKBIA — BTRC (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: NFKBIA — BTRC (direct interaction, pull down)
  • IRef Biogrid Interaction: NFKBIA — BTRC (direct interaction, enzymatic study)
  • IRef Biogrid Interaction: CTNNB1 — SKP1 (direct interaction, unspecified method)
  • IRef Biogrid Interaction: BTRC — SKP1 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: BTRC — SKP1 (direct interaction, pull down)
  • IRef Biogrid Interaction: CUL1 — SKP1 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: NFKBIA — SKP1 (direct interaction, unspecified method)
  • IRef Biogrid Interaction: CTNNB1 — BTRC (direct interaction, unspecified method)
  • IRef Biogrid Interaction: CUL1 — BTRC (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: BTRC — NFKB1 (direct interaction, pull down)
  • IRef Biogrid Interaction: BTRC — NFKB1 (physical association, affinity chromatography technology)
  • MIPS CORUM Ubiquitin E3 ligase (SKP1A, BTRC, CUL1): Ubiquitin E3 ligase (SKP1A, BTRC, CUL1) complex (BTRC-CUL1-SKP1)
  • IRef Hprd Interaction: Complex of 19 proteins (in vivo)
  • Reactome Reaction: RBX1 → APC (indirect_complex)
  • Reactome Reaction: NFKBIE → CUL1 (reaction)
  • Reactome Reaction: AXIN1 → SKP1 (indirect_complex)
  • Reactome Reaction: REL → CUL1 (reaction)
  • Reactome Reaction: AXIN1 → SKP1 (reaction)
  • Reactome Reaction: RBX1 → AMER1 (indirect_complex)
  • Reactome Reaction: CTNNB1 → RBX1 (indirect_complex)
  • Reactome Reaction: CTNNB1 → SKP1 (reaction)
  • Reactome Reaction: SKP1 → AMER1 (reaction)
  • Reactome Reaction: NFKBIB → SKP1 (indirect_complex)
  • Reactome Reaction: NFKBIA → SKP1 (reaction)
  • Reactome Reaction: CTNNB1 → RBX1 (reaction)
  • Reactome Reaction: BTRC → NFKBIB (reaction)
  • Reactome Reaction: RBX1 → GSK3B (reaction)
  • Reactome Reaction: CTNNB1 → BTRC (indirect_complex)
  • Reactome Reaction: FBXW11 → NFKB1 (indirect_complex)
  • Reactome Reaction: CSNK1A1 → RBX1 (indirect_complex)
  • Reactome Reaction: CSNK1A1 → SKP1 (indirect_complex)
  • Reactome Reaction: FBXW11 → REL (indirect_complex)
  • Reactome Reaction: CTNNB1 → BTRC (reaction)
  • Reactome Reaction: BTRC → NFKBIA (indirect_complex)
  • Reactome Reaction: REL → CUL1 (indirect_complex)
  • Reactome Reaction: BTRC → NFKB1 (indirect_complex)
  • Reactome Reaction: AXIN1 → CUL1 (reaction)
  • Reactome Reaction: SKP1 → GSK3B (reaction)
  • Reactome Reaction: FBXW11 → RELA (indirect_complex)
  • Reactome Reaction: CTNNB1 → SKP1 (indirect_complex)
  • Reactome Reaction: CUL1 → AMER1 (reaction)
  • Reactome Reaction: BTRC → AMER1 (reaction)
  • Reactome Reaction: AXIN1 → RBX1 (reaction)
  • Reactome Reaction: BTRC → RELA (indirect_complex)
  • Reactome Reaction: REL → SKP1 (indirect_complex)
  • Reactome Reaction: BTRC → REL (reaction)
  • Reactome Reaction: BTRC → NFKBIE (indirect_complex)
  • Reactome Reaction: NFKBIA → CUL1 (reaction)
  • Reactome Reaction: BTRC → RELA (reaction)
  • Reactome Reaction: BTRC → REL (indirect_complex)
  • Reactome Reaction: CSNK1A1 → CUL1 (reaction)
  • Reactome Reaction: FBXW11 → NFKBIA (indirect_complex)
  • Reactome Reaction: BTRC → APC (indirect_complex)
  • Reactome Reaction: CUL1 → GSK3B (reaction)
  • Reactome Reaction: NFKBIA → CUL1 (indirect_complex)
  • Reactome Reaction: NFKBIB → CUL1 (reaction)
  • Reactome Reaction: RELA → SKP1 (reaction)
  • Reactome Reaction: SKP1 → APC (indirect_complex)
  • Reactome Reaction: FBXW11 → REL (reaction)
  • Reactome Reaction: FBXW11 → NFKBIA (reaction)
  • Reactome Reaction: SKP1 → GSK3B (indirect_complex)
  • Reactome Reaction: NFKBIB → SKP1 (reaction)
  • Reactome Reaction: CUL1 → APC (indirect_complex)
  • Reactome Reaction: CUL1 → APC (reaction)
  • Reactome Reaction: NFKB1 → CUL1 (reaction)
  • Reactome Reaction: SKP1 → APC (reaction)
  • Reactome Reaction: CSNK1A1 → CUL1 (indirect_complex)
  • Reactome Reaction: BTRC → GSK3B (indirect_complex)
  • Reactome Reaction: FBXW11 → NFKBIE (indirect_complex)
  • Reactome Reaction: BTRC → NFKB1 (reaction)
  • Reactome Reaction: NFKBIA → SKP1 (indirect_complex)
  • Reactome Reaction: NFKBIE → SKP1 (reaction)
  • Reactome Reaction: BTRC → NFKBIE (reaction)
  • Reactome Reaction: RELA → SKP1 (indirect_complex)
  • Reactome Reaction: RBX1 → APC (reaction)
  • Reactome Reaction: RELA → CUL1 (reaction)
  • Reactome Reaction: CTNNB1 → CUL1 (indirect_complex)
  • Reactome Reaction: BTRC → APC (reaction)
  • Reactome Reaction: CUL1 → GSK3B (indirect_complex)
  • Reactome Reaction: FBXW11 → RELA (reaction)
  • Reactome Reaction: RBX1 → GSK3B (indirect_complex)
  • Reactome Reaction: FBXW11 → NFKBIE (reaction)
  • Reactome Reaction: BTRC → GSK3B (reaction)
  • Reactome Reaction: FBXW11 → NFKB1 (reaction)
  • Reactome Reaction: SKP1 → AMER1 (indirect_complex)
  • Reactome Reaction: FBXW11 → NFKBIB (reaction)
  • Reactome Reaction: AXIN1 → RBX1 (indirect_complex)
  • Reactome Reaction: AXIN1 → CUL1 (indirect_complex)
  • Reactome Reaction: CSNK1A1 → RBX1 (reaction)
  • Reactome Reaction: BTRC → CSNK1A1 (reaction)
  • Reactome Reaction: CUL1 → AMER1 (indirect_complex)
  • Reactome Reaction: CSNK1A1 → SKP1 (reaction)
  • Reactome Reaction: BTRC → CSNK1A1 (indirect_complex)
  • Reactome Reaction: BTRC → AMER1 (indirect_complex)
  • Reactome Reaction: FBXW11 → NFKBIB (indirect_complex)
  • Reactome Reaction: NFKBIE → SKP1 (indirect_complex)
  • Reactome Reaction: RBX1 → AMER1 (reaction)
  • Reactome Reaction: AXIN1 → BTRC (reaction)
  • Reactome Reaction: NFKBIE → CUL1 (indirect_complex)
  • Reactome Reaction: CTNNB1 → CUL1 (reaction)
  • Reactome Reaction: AXIN1 → BTRC (indirect_complex)
  • Reactome Reaction: REL → SKP1 (reaction)
  • Reactome Reaction: RELA → CUL1 (indirect_complex)
  • Reactome Reaction: BTRC → NFKBIA (reaction)
  • Reactome Reaction: NFKB1 → SKP1 (reaction)
  • Reactome Reaction: NFKB1 → SKP1 (indirect_complex)
  • Reactome Reaction: NFKBIB → CUL1 (indirect_complex)
  • Reactome Reaction: NFKB1 → CUL1 (indirect_complex)
  • Reactome Reaction: BTRC → NFKBIB (indirect_complex)
In total, 51 gene pairs are associated to this article in curated databases