The Repressing Function of the Oncoprotein BCL-3 Requires CtBP, while Its Polyubiquitination and Degradation Involve the E3 Ligase TBLR1
- 1 August 2010
- journal article
- research article
- Published by Taylor & Francis Ltd in Molecular and Cellular Biology
- Vol. 30 (16), 4006-4021
- https://doi.org/10.1128/mcb.01600-09
Abstract
The nuclear and oncogenic BCL-3 protein activates or represses gene transcription when bound to NF-kappa B 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 kappa B protein, and they establish a functional link between the E3 ligase TBLR1 and NF-kappa B.This publication has 52 references indexed in Scilit:
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