Siah-1, SIP, and Ebi Collaborate in a Novel Pathway for Beta-Catenin Degradation Linked to p53 Responses

Mol Cell. 2001 May;7(5):915-26. doi: 10.1016/s1097-2765(01)00242-8.

Abstract

Destruction of beta-catenin is regulated through phosphorylation-dependent interactions with the F box protein beta-TrCP. A novel pathway for beta-catenin degradation was discovered involving mammalian homologs of Drosophila Sina (Siah), which bind ubiquitin-conjugating enzymes, and Ebi, an F box protein that binds beta-catenin independent of the phosphorylation sites recognized by beta-TrCP. A series of protein interactions were identified in which Siah is physically linked to Ebi by association with a novel Sgt1 homolog SIP that binds Skp1, a central component of Skp1-Cullin-F box complexes. Expression of Siah is induced by p53, revealing a way of linking genotoxic injury to destruction of beta-catenin, thus reducing activity of Tcf/LEF transcription factors and contributing to cell cycle arrest.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Calcium-Binding Proteins*
  • Carrier Proteins / physiology*
  • Cell Cycle / drug effects
  • Cell Cycle Proteins*
  • Cytoskeletal Proteins / drug effects
  • Cytoskeletal Proteins / metabolism*
  • DNA Damage / physiology
  • DNA-Binding Proteins / drug effects
  • DNA-Binding Proteins / metabolism
  • Drosophila Proteins*
  • GTP-Binding Proteins*
  • Heat-Shock Proteins*
  • Humans
  • Insect Proteins / metabolism
  • Insect Proteins / pharmacology
  • Insect Proteins / physiology*
  • Lymphoid Enhancer-Binding Factor 1
  • Molecular Sequence Data
  • Nuclear Proteins / metabolism
  • Nuclear Proteins / pharmacology
  • Nuclear Proteins / physiology*
  • Protein Binding
  • Sequence Alignment
  • Signal Transduction / drug effects
  • Trans-Activators*
  • Transcription Factors / drug effects
  • Transcription Factors / metabolism
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / pharmacology*
  • Tumor Suppressor Protein p53 / physiology
  • Two-Hybrid System Techniques
  • Ubiquitin-Protein Ligases
  • beta Catenin

Substances

  • CACYBP protein, human
  • CTNNB1 protein, human
  • Calcium-Binding Proteins
  • Carrier Proteins
  • Cell Cycle Proteins
  • Cytoskeletal Proteins
  • DNA-Binding Proteins
  • Drosophila Proteins
  • Heat-Shock Proteins
  • Insect Proteins
  • Lymphoid Enhancer-Binding Factor 1
  • Nuclear Proteins
  • Trans-Activators
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • beta Catenin
  • ebi protein, Drosophila
  • Ubiquitin-Protein Ligases
  • seven in absentia proteins
  • GTP-Binding Proteins