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Nuclear phosphoinositides and their impact on nuclear functions
Author(s) -
Shah Zahid H.,
Jones David R.,
Sommer Lilly,
Foulger Rebecca,
Bultsma Yvette,
D'Santos Clive,
Divecha Nullin
Publication year - 2013
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.12543
Subject(s) - biology , microbiology and biotechnology , transcription factor , nuclear localization sequence , chromatin , nuclear transport , cell nucleus , nucleus , genetics , dna , gene
Polyphosphoinositides ( PPI n) are important lipid molecules whose levels are de‐regulated in human diseases such as cancer, neurodegenerative disorders and metabolic syndromes. PPI n are synthesized and degraded by an array of kinases, phosphatases and lipases which are localized to various subcellular compartments and are subject to regulation in response to both extra‐ and intracellular cues. Changes in the activities of enzymes that metabolize PPI n lead to changes in the profiles of PPI n in various subcellular compartments. Understanding how subcellular PPI n are regulated and how they affect downstream signaling is critical to understanding their roles in human diseases. PPI n 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 PPI n affect. Over recent years, targeted and global proteomic studies have identified a plethora of potential PPI n‐interacting proteins involved in many aspects of transcription, chromatin remodelling and m RNA maturation, suggesting that PPI n signalling within the nucleus represents a largely unexplored novel layer of complexity in the regulation of nuclear functions.