Nuclear PI3K Signaling in Cell Growth and Tumorigenesis
REVIEW published: 13 April 2015 doi: 10.3389/fcell.2015.00024 Nuclear PI3K signaling in cell growth and tumorigenesis William J. Davis, Peter Z. Lehmann and Weimin Li * College of Medical Sciences, Washington State University, Spokane, WA, USA The PI3K/Akt signaling pathway is a major driving force in a variety of cellular functions. Dysregulation of this pathway has been implicated in many human diseases including cancer. While the activity of the cytoplasmic PI3K/Akt pathway has been extensively studied, the functions of these molecules and their effector proteins within the nucleus are poorly understood. Harboring key cellular processes such as DNA replication and repair as well as nascent messenger RNA transcription, the nucleus provides a unique compartmental environment for protein–protein and protein–DNA/RNA interactions required for cell survival, growth, and proliferation. Here we summarize recent advances made toward elucidating the nuclear PI3K/Akt signaling cascade and its key components within the nucleus as they pertain to cell growth and tumorigenesis. This review covers Edited by: the spatial and temporal localization of the major nuclear kinases having PI3K activities Massimo Mattia Santoro, and the counteracting phosphatases as well as the role of nuclear PI3K/Akt signaling in University of Leuven, Belgium mRNA processing and exportation, DNA replication and repair, ribosome biogenesis, cell Reviewed by: Emilio Hirsch, survival, and tumorigenesis. University of Torino, Italy Keywords: nuclear signaling, PI3K/Akt/mTOR, cell growth, tumorigenesis, ribosome biogenesis, cell survival, DNA Andrea Graziani, damage, mRNA processing and export Università VIta-Salute San Raffaele, Italy *Correspondence: Introduction Weimin Li, College of Medical Sciences, Washington State University, 412 E In the late 1970s and early 1980s, the existence of a nuclear phosphatidylinositol (PtdIns) cycle Spokane Falls Blvd., Spokane 99202 was proposed (Manzoli et al., 1978, 1982).
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