RBBP6 interacts with multifunctional protein YB-1 through its RING finger domain, leading to ubiquitination and proteosomal degradation of YB-1.
RBBP6 (retinoblastoma binding protein 6) is a 250-kDa multifunctional protein that interacts with both p53 and pRb and has been implicated in mRNA processing. It has also been identified as a putative E3 ubiquitin ligase due to the presence of a RING finger domain, although no substrate has been identified ... up to now. Using the RING finger domain as bait in a yeast two-hybrid screen, we identified YB-1 (Y-box binding protein 1) as a binding partner of RBBP6, localising the interaction to the last 62 residues of YB-1. We showed, furthermore, that both full-length RBBP6 and the isolated RING finger domain were able to ubiquitinate YB-1, resulting in its degradation in the proteosome. As a result, RBBP6 was able to suppress the levels of YB-1 in vivo and to reduce its transactivational ability. In the light of the important role that YB-1 appears to play in tumourigenesis, our results suggest that RBBP6 may be a relevant target for therapeutic drugs aimed at modifying the activity of YB-1.
Mesh Terms:
Carrier Proteins, Cell Line, DNA-Binding Proteins, Humans, Nuclear Proteins, Proteasome Endopeptidase Complex, Protein Binding, Protein Interaction Domains and Motifs, Protein Interaction Mapping, RING Finger Domains, Two-Hybrid System Techniques, Ubiquitination
Carrier Proteins, Cell Line, DNA-Binding Proteins, Humans, Nuclear Proteins, Proteasome Endopeptidase Complex, Protein Binding, Protein Interaction Domains and Motifs, Protein Interaction Mapping, RING Finger Domains, Two-Hybrid System Techniques, Ubiquitination
J. Mol. Biol.
Date: Dec. 26, 2008
PubMed ID: 18851979
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- Interactions 14
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