title: Interactions of cullin3/KCTD5 complexes with both cytoplasmic and nuclear proteins: Evidence for a role in protein stabilization.
abstract: Based on its specific interaction with cullin3 mediated by an N-terminal BTB/POZ homologous domain, KCTD5 has been proposed to function as substrate adapter for cullin3 based ubiquitin E3 ligases. In the present study we tried to validate this hypothesis through identification and characterization of additional KCTD5 interaction partners. For the replication protein MCM7, the zinc finger protein ZNF711 and FAM193B, a yet poorly characterized cytoplasmic protein, we could demonstrate specific interaction with KCTD5 both in yeast two-hybrid and co-precipitation studies in mammalian cells. Whereas trimeric complexes of cullin3 and KCTD5 with the respective KCTD5 binding partner were formed, KCTD5/cullin3 induced polyubiquitylation and/or proteasome-dependent degradation of these binding partners could not be demonstrated. On the contrary, KCTD5 or Cullin3 overexpression increased ZNF711 protein stability.
authors.affiliation: Institute of Virology, Campus Benjamin Franklin, Charité-University Medicine Berlin, Berlin, Germany.
authors.forename: Natalja
authors.initials: N
authors.lastname: Rutz
authors.affiliation: Institute of Virology, Campus Benjamin Franklin, Charité-University Medicine Berlin, Berlin, Germany.
authors.forename: Regine
authors.initials: R
authors.lastname: Heilbronn
authors.affiliation: Institute of Virology, Campus Benjamin Franklin, Charité-University Medicine Berlin, Berlin, Germany. Electronic address: stefan.weger@charite.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Weger
mesh_terms: D002455:Cell Division; D044842:Cullin Proteins / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells / Q000378:metabolism; D006801:Humans; D064168:Minichromosome Maintenance Complex Component 7 / Q000235:genetics / Q000378:metabolism; D046912:Multiprotein Complexes / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D025941:Protein Interaction Mapping; D055550:Protein Stability; D021381:Protein Transport; D020798:Two-Hybrid System Techniques; D054875:Ubiquitination
chemical_list: C503645:CUL3 protein, human; D044842:Cullin Proteins; D004268:DNA-Binding Proteins; C558647:FAM193B protein, human; C521187:KCTD5 protein, human; D046912:Multiprotein Complexes; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D015221:Potassium Channels; C484727:ZNF711 protein, human; C101624:MCM7 protein, human; D064168:Minichromosome Maintenance Complex Component 7
keywords: BTB domain; E3 ubiquitin ligase; KCTD5; MCM7; Protein stabilization; ZNF711