Protein phosphorylation as a key mechanism for the regulation of BCL-3 activity.
Constitutive NF-kappaB 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-kappaB activity is the result of point mutations or translocations of the genes coding for NF-kappaB inhibitors, namely IkappaBalpha or p100. The BCL-3 protein is another member of the IkappaB 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-kappaB/IkappaB protein phosphorylations is critical in order to better understand the molecular mechanisms of NF-kappaB-mediated oncogenesis.
Viatour
Patrick
P
Laboratory of Medical Chemistry and Human Genetics, Center for Biomedical Integrated Genoproteomics, University of Liège, Sart-Tilman, Liège, Belgium.
Merville
Marie-Paule
MP
Bours
Vincent
V
Chariot
Alain
A
D000818:Animals; D000081242:B-Cell Lymphoma 3 Protein; D005786:Gene Expression Regulation; D006801:Humans; D008954:Models, Biological; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D014158:Transcription, Genetic
D000081242:B-Cell Lymphoma 3 Protein; C000631344:BCL3 protein, human; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors