Nuclear phosphoinositides and their impact on nuclear functions.

Abstract

Polyphosphoinositides (PPIn) are important lipid molecules whose levels are deregulated in human diseases such as cancer, neurodegenerative and in metabolic syndromes. PPIn are synthesised and degraded by an array of kinases, phosphatases and lipases which are localised to various subcellular compartments and are subject to regulation in response to both extra- and intracellular cues. Changes in the activities of enzymes that metabolise PPIn lead to changes in the profiles of PPIn in different sub-cellular compartments. Understanding how subcellular PPIn are regulated and how they impact on downstream signaling is critical to understand their roles in human diseases. PPIn are present in the nucleus, and their levels are changed in response to various stimuli, suggesting that they may serve to regulate specific nuclear functions. However, the lack of nuclear downstream targets has hindered the definition of which pathways nuclear PPIn impact on. Over recent years targeted and global proteomic studies have identified a plethora of potential PPIn interacting proteins involved in many aspects of transcription, chromatin remodeling and mRNA maturation suggesting that PPIn signaling within the nucleus represents a largely unexplored novel layer of complexity in the regulation of nuclear functions. This article is protected by copyright. All rights reserved.