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, James A; Rakus, Dariusz; Gizak, Agnieszka; Steelman, Linda S; Abrams, Steve L; Lertpiriyapong, Kvin; Fitzgerald, Timothy L; Yang, Li V; Montalto, Giuseppe; Cervello, Melchiorre; Libra, Massimo; Nicoletti, Ferdinando; Scalisi, Aurora; Torino, Francesco; Fenga, Concettina; Neri, Luca M; Marmiroli, Sandra; Cocco, Lucio; Martelli, Alberto M.. - In: BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH. - ISSN 0167-4889. - 1863:12(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

MARMIROLI, Sandra;
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.
6-set-2016
1863
12
2942
2976
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, James A; Rakus, Dariusz; Gizak, Agnieszka; Steelman, Linda S; Abrams, Steve L; Lertpiriyapong, Kvin; Fitzgerald, Timothy L; Yang, Li V; Montalto, Giuseppe; Cervello, Melchiorre; Libra, Massimo; Nicoletti, Ferdinando; Scalisi, Aurora; Torino, Francesco; Fenga, Concettina; Neri, Luca M; Marmiroli, Sandra; Cocco, Lucio; Martelli, Alberto M.. - In: BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH. - ISSN 0167-4889. - 1863:12(2016), pp. 2942-2976. [10.1016/j.bbamcr.2016.09.004]
Mccubrey, James A; Rakus, Dariusz; Gizak, Agnieszka; Steelman, Linda S; Abrams, Steve L; Lertpiriyapong, Kvin; Fitzgerald, Timothy L; Yang, Li V; Montalto, Giuseppe; Cervello, Melchiorre; Libra, Massimo; Nicoletti, Ferdinando; Scalisi, Aurora; Torino, Francesco; Fenga, Concettina; Neri, Luca M; Marmiroli, Sandra; Cocco, Lucio; Martelli, Alberto M.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11380/1132170
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