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.

Mccubrey, J., Rakus, D., Gizak, A., Steelman, L., Abrams, S., Lertpiriyapong, K., et al. (2016). Effects of mutations in Wnt/β-catenin, hedgehog, Notch and PI3K pathways on GSK-3 activity—Diverse effects on cell growth, metabolism and cancer. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 1863(12), 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

TORINO, FRANCESCO;
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.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/06 - Oncologia Medica
English
Con Impact Factor ISI
Akt; GSK-3; Hedgehog; Notch; PI3K; Targeted therapy; Therapy resistance; Wnt/beta-catenin; mTOR
Mccubrey, J., Rakus, D., Gizak, A., Steelman, L., Abrams, S., Lertpiriyapong, K., et al. (2016). Effects of mutations in Wnt/β-catenin, hedgehog, Notch and PI3K pathways on GSK-3 activity—Diverse effects on cell growth, metabolism and cancer. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 1863(12), 2942-2976 [10.1016/j.bbamcr.2016.09.004].
Mccubrey, J; Rakus, D; Gizak, A; Steelman, L; Abrams, S; Lertpiriyapong, K; Fitzgerald, T; Yang, L; Montalto, G; Cervello, M; Libra, M; Nicoletti, F; Scalisi, A; Torino, F; Fenga, C; Neri, L; Marmiroli, S; Cocco, L; Martelli, A
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/171362
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