CREB in long-term potentiation in hippocampus: role of post-translational modifications-studies In silico

The multifunctionality of proteins is dictated by post-translational modifications (PTMs) which involve the attachment of small functional groups such as phosphate and acetate, as well as carbohydrate moieties. These functional groups make the protein perform various functions in different environments. PTMs play a crucial role in memory and learning. Phosphorylation of synaptic proteins and transcription factors regulate the generation and storage of memory. Among these is the cAMP-regulated element binding protein CREB that regulates CRE containing genes like c-fos. Both phosphorylation and acetylation control the function of CREB as a transcription factor. CREB is also susceptible to O-GlcNAc modification, which inhibits its activity. O-GlcNAc modification occurs on the same or neighboring Ser/Thr residues akin to phosphorylation. An interplay between these modifications was shown to operate in nuclear and cytoplasmic proteins. In this study computational methods were utilized to predict different modification sites in CREB. These in silico results suggest that phosphorylation, O-GlcNAc modification and acetylation modulate the transcriptional activity of CREB and thus dictate its contribution to synaptic plasticity.