Protein phosphorylation as a key mechanism for the regulation of BCL-3 activity

Abstract

Constitutive NF-κB activation, a hallmark of many human cancers, upregulates anti-apoptotic gene expression and therefore disrupts the balance between apoptosis and proliferation. In some lymphomas, this constitutive NF-κB activity is the result of point mutations or translocations of the genes coding for NF-κB inhibitors, namely IκBα or p100. The BCL-3 protein is another member of the IκB family and is overexpressed in a subset of human B-cell chronic lymphocytic leukemias because of a chromosomal translocation. This oncoprotein is phosphorylated by multiple kinases including GSK3 and this phosphorylation regulates BCL-3 function by modulating its oncogenic potential and by regulating the expression of a subset of its target genes. Therefore, deciphering the NF-κB/IκB protein phosphorylations is critical in order to better understand the molecular mechanisms of NF-κB-mediated oncogenesis. ©2004 Landes Bioscience.