Cancer Res 2015[Sep]; 75 (18): 3692-5 PMID26337909show ga
In normal cells exposed to stress, the central transcription factor nuclear factor ?B (NF-?B) is activated only transiently, to modulate the activation of downstream immune responses. However, in most cancers, NF-?B is abnormally activated constitutively, contributing thus to oncogenesis and tumor progression. Therefore, down regulating NF-?B activity is an important goal of cancer treatment. In order to control NF-?B activity therapeutically, it is helpful to understand the molecular mechanisms that normally govern its activation, and how dysregulated NF-?B activity may aid the development of disease. Recent evidence from our labs (1-4) and others (5-7) indicates that, in addition to various post-translational modifications of NF-?B that have been observed previously, including phosphorylation, ubiquitination, and acetylation, NF-?B can be methylated reversibly on lysine or arginine residues by histone modifying enzymes, including lysine and arginine methyl transferases and demethylases. Furthermore, these methylations are required to activate many downstream genes. Interestingly, amplifications and mutations of several such enzymes have been linked to cancer. We propose that some of these mutations may alter the methylation not only of histones but also of NF-?B, making them attractive therapeutic targets.
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Cancer+Res 2015 ; 75 (18): 3692-5
