Phosphoinositide 3-kinase signalling in the nucleolus.

The phosphoinositide 3-kinase (PI3K) signalling pathway plays key roles in many cellular processes and is altered in many diseases. The function and mode of action of the pathway have mostly been elucidated in the cytoplasm. However, many of the components of the PI3K pathway are also present in the nucleus at specific sub-nuclear sites including nuclear speckles, nuclear lipid islets and the nucleolus.

Nuclear Phosphatidylinositol 3,4,5-Trisphosphate Interactome Uncovers an Enrichment in Nucleolar Proteins.

Polyphosphoinositides (PPIns) play essential roles as lipid signaling molecules, and many of their functions have been elucidated in the cytoplasm. However, PPIns are also intranuclear where they contribute to chromatin remodeling, transcription, and mRNA splicing. The PPIn, phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P), has been mapped to the nucleus and nucleoli, but its role remains unclear in this subcellular compartment.

Nuclear upregulation of class I phosphoinositide 3-kinase p110β correlates with high 47S rRNA levels in cancer cells.

The class I phosphoinositide 3-kinase (PI3K) catalytic subunits p110α and p110β are ubiquitously expressed but differently targeted in tumours. In cancer, (encoding p110β) is seldom mutated compared with (encoding p110α) but can contribute to tumorigenesis in certain PTEN-deficient tumours. The underlying molecular mechanisms are, however, unclear.