TY - JOUR
T1 - Effects of mutations in Wnt/β-catenin, hedgehog, Notch and PI3K pathways on GSK-3 activity-Diverse effects on cell growth, metabolism and cancer
AU - Montalto, Giuseppe
AU - Yang, Li V
AU - Cervello, Melchiorre
AU - Martelli, Alberto M
AU - Fenga, Concettina
AU - Fitzgerald, Timothy L
AU - Nicoletti, Ferdinando
AU - Abrams, Steve L
AU - Gizak, Agnieszka
AU - Lertpiriyapong, Kvin
AU - Scalisi, Aurora
AU - Rakus, Dariusz
AU - Marmiroli, Sandra
AU - Libra, Massimo
AU - Steelman, Linda S
AU - Mccubrey, James A
AU - Neri, Luca M
AU - Cocco, Lucio
AU - Montalto, Giuseppe
AU - Abrams, Steve L
AU - Torino, Francesco
PY - 2016
Y1 - 2016
N2 - Glycogen synthase kinase-3 (GSK-3) is a serine/threonine kinase that participates in an array of critical cellular processes. GSK-3 was first characterized as an enzyme that phosphorylated and inactivated glycogen synthase. However, subsequent studies have revealed that this moon-lighting protein is involved in numerous signaling pathways that regulate not only metabolism but also have roles in: apoptosis, cell cycle progression, cell renewal, differentiation, embryogenesis, migration, regulation of gene transcription, stem cell biology and survival. In this review, we will discuss the roles that GSK-3 plays in various diseases as well as how this pivotal kinase interacts with multiple signaling pathways such as: PI3K/PTEN/Akt/mTOR, Ras/Raf/MEK/ERK, Wnt/beta-catenin, hedgehog, Notch and TP53. Mutations that occur in these and other pathways can alter the effects that natural GSK-3 activity has on regulating these signaling circuits that can lead to cancer as well as other diseases. The novel roles that microRNAs play in regulation of the effects of GSK-3 will also be evaluated. Targeting GSK-3 and these other pathways may improve therapy and overcome therapeutic resistance.
AB - Glycogen synthase kinase-3 (GSK-3) is a serine/threonine kinase that participates in an array of critical cellular processes. GSK-3 was first characterized as an enzyme that phosphorylated and inactivated glycogen synthase. However, subsequent studies have revealed that this moon-lighting protein is involved in numerous signaling pathways that regulate not only metabolism but also have roles in: apoptosis, cell cycle progression, cell renewal, differentiation, embryogenesis, migration, regulation of gene transcription, stem cell biology and survival. In this review, we will discuss the roles that GSK-3 plays in various diseases as well as how this pivotal kinase interacts with multiple signaling pathways such as: PI3K/PTEN/Akt/mTOR, Ras/Raf/MEK/ERK, Wnt/beta-catenin, hedgehog, Notch and TP53. Mutations that occur in these and other pathways can alter the effects that natural GSK-3 activity has on regulating these signaling circuits that can lead to cancer as well as other diseases. The novel roles that microRNAs play in regulation of the effects of GSK-3 will also be evaluated. Targeting GSK-3 and these other pathways may improve therapy and overcome therapeutic resistance.
UR - http://hdl.handle.net/10447/199956
M3 - Article
VL - 1863
SP - 2942
EP - 2976
JO - BIOCHIMICA ET BIOPHYSICA ACTA. MOLECULAR CELL RESEARCH
JF - BIOCHIMICA ET BIOPHYSICA ACTA. MOLECULAR CELL RESEARCH
SN - 1879-2596
ER -