The repressing function of the oncoprotein BCL-3 requires CtBP, while its polyubiquitination and degradation involve the E3 ligase TBLR1.

The nuclear and oncogenic BCL-3 protein activates or represses gene transcription when bound to NF-kappaB proteins p50 and p52, yet the molecules that specifically interact with BCL-3 and drive BCL-3-mediated effects on gene expression remain largely uncharacterized. Moreover, GSK3-mediated phosphorylation of BCL-3 triggers its degradation through the proteasome, but the ...
proteins involved in this degradative pathway are poorly characterized. Biochemical purification of interacting partners of BCL-3 led to the identification of CtBP as a molecule required for the ability of BCL-3 to repress gene transcription. CtBP is also required for the oncogenic potential of BCL-3 and for its ability to inhibit UV-mediated cell apoptosis in keratinocytes. We also defined the E3 ligase TBLR1 as a protein involved in BCL-3 degradation through a GSK3-independent pathway. Thus, our data demonstrate that the LSD1/CtBP complex is required for the repressing abilities of an oncogenic I kappaB protein, and they establish a functional link between the E3 ligase TBLR1 and NF-kappaB.
Mesh Terms:
Alcohol Oxidoreductases, Animals, Cell Line, DNA-Binding Proteins, Glycogen Synthase Kinase 3, Hela Cells, Histone Demethylases, Humans, Mice, NF-kappa B, NIH 3T3 Cells, Oxidoreductases, N-Demethylating, Protein Interaction Domains and Motifs, Protein Stability, Proto-Oncogene Proteins, Recombinant Proteins, Repressor Proteins, Transcription Factors, Ubiquitin-Protein Ligases, Ubiquitination
Mol. Cell. Biol.
Date: Aug. 01, 2010
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