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.
Effects of mutations in Wnt/β-Catenin, Hedgehog, Notch and PI3K pathways on GSK-3 activity—diverse effects on cell growth, metabolism and cancer / Mccubrey, J.A.; Rakus, D.; Gizak, A.; Steelman, L.S.; Abrams, S.L.; Lertpiriyapong, K.; Fitzgerald, T.; Yang, L.; Montalto, G.; Cervello, M.; Libra, M.; Nicoletti, F.; Scalisi, A.; Fenga, C.; Marmiroli, S.; Neri, L.M.; Cocco, L.; Martelli, A.M. .. - In: BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH. - ISSN 0167-4889. - STAMPA. - 1863:(2016), pp. 2942-2976. [10.1016/j.bbamcr.2016.09.004]
Effects of mutations in Wnt/β-Catenin, Hedgehog, Notch and PI3K pathways on GSK-3 activity—diverse effects on cell growth, metabolism and cancer.
COCCO, LUCIO ILDEBRANDO;MARTELLI, ALBERTO MARIA
2016
Abstract
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
