Post-translational modifications of C/EBP-β: Jack of all trades, master of some

Abstract

CCAAT/Enhancer binding protein-beta (C/EBP-beta) is a member of the C/EBP family of basic leucine zipper transcription factors. C/EBP-beta is imperative to the processes of differentiation, proliferation and inflammation in a number of cell types. As a master regulator, its expression and activity have to be tightly controlled at the transcriptional, translational and the posttranslational level. Recent developments in the research of histone and non-histone proteins has increased the attention for post-translational regulation. This has resulted in the identification of numerous protein targets and various novel post-translational modifications. The reversible enzymatic attachment of post-translational modifications to their target residues is mediated by so called ‘writers’ and ‘erasers’. C/EBP-beta is subject to four currently recognized posttranslational modifications: phosphorylation, sumoylation, acetylation and methylation. These interacting post-translational modifications influence, DNA-binding, protein conformation, protein-protein interactions and nuclear localization. However, the downstream mechanisms through which these modifications operate are largely unknown. Similar to the ‘histone code’, the combined post-translational modifications on non-histone proteins have been hypothesized to constitute a functional ‘protein code’, which is interpreted by specific proteins termed ‘readers’. The existence of a code on C/EBP-beta and possibly other proteins appears improbable as differential effects have been reported. The downstream events are more likely to be dependent on the cellular context, determining the interpretation through expression of distinct subsets of ‘reader’ proteins. Nonetheless, post-translational modification of C/EBP-beta is vital to its regulation in numerous cellular and physiological processes. Further research is required to elucidate the exact mechanism through which post-translational modifications modulate C/EBP-beta function.