Diagenode

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


Keutgens A, Shostak K, Close P, Zhang X, Hennuy B, Aussems M, Chapelle JP, Viatour P, Gothot A, Fillet M, Chariot A

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.

Tags
Bioruptor
Chromatin Shearing
ChIP-qPCR

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Published
August, 2010

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