Novel functions of chromatin-bound I kappa B alpha in oncogenic transformation

作者：Espinosa L^*; Bigas A; Mulero M C

来源：British Journal of Cancer, 2014, 111(9): 1688-1692.

DOI：10.1038/bjc.2014.84

• I kappa B alpha
• SUMO
• Polycomb
• Tumour Necrosis Factor (TNF alpha)
• Squamous Cell Carcinoma (SCC)

The nuclear factor-kappa B (NF-kappa B) signalling pathway participates in a multitude of biological processes, which imply the requirement of a complex and precise regulation. I kappa B (for Inhibitor of kappaB) proteins, which bind and retain NF-kappa B dimers in the cytoplasm, are the main contributors to negative regulation of NF-kappa B under non-stimulation conditions. Nevertheless, increasing evidences indicate that I kappa B proteins exert specific nuclear roles that directly contribute to the control of gene transcription. In particular, hypophosphorylated I kappa B beta can bind the promoter region of TNF alpha leading to persistent gene transcription in macrophages and contributing to the regulation of the inflammatory response. Recently, we demonstrated that phosphorylated and SUMOylated I kappa B alpha reside in the nucleus of the cells where it binds to chromatin leading to specific transcriptional repression. Mechanistically, I kappa B alpha associates and regulates Polycomb Repressor Complex activity, a function that is evolutionary conserved from flies to mammals, as indicate the homeotic phenotype of Drosophila mutants. Here we discuss the implications of chromatin-bound I kappa B alpha function in the context of tumorigenesis.

• 出版日期2014-10-28