Siah-1, SIP, and Ebi collaborate in a novel pathway for beta-catenin degradation linked to p53 responses.
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.
Matsuzawa
S I
SI
The Burnham Institute, 10901 N. Torrey Pines Road, La Jolla, CA 92037, USA.
Reed
J C
JC
D000595:Amino Acid Sequence; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins / Q000502:physiology*; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins / Q000187:drug effects / Q000378:metabolism*; D004249:DNA Damage / Q000502:physiology; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D029721:Drosophila Proteins; D019204:GTP-Binding Proteins; D006360:Heat-Shock Proteins; D006801:Humans; D019476:Insect Proteins / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D051821:Lymphoid Enhancer-Binding Factor 1; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D011485:Protein Binding; D016415:Sequence Alignment; D015398:Signal Transduction / Q000187:drug effects; D015534:Trans-Activators; D014157:Transcription Factors / Q000187:drug effects / Q000378:metabolism; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000494:pharmacology* / Q000502:physiology; D020798:Two-Hybrid System Techniques; D044767:Ubiquitin-Protein Ligases; D051176:beta Catenin; D000098563:Seven in Absentia Proteins
C491778:CACYBP protein, human; C495270:CTNNB1 protein, human; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D006360:Heat-Shock Proteins; D019476:Insect Proteins; D051821:Lymphoid Enhancer-Binding Factor 1; D009687:Nuclear Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D051176:beta Catenin; C119014:ebi protein, Drosophila; D044767:Ubiquitin-Protein Ligases; D000098563:Seven in Absentia Proteins; D019204:GTP-Binding Proteins