Effects of mutations in Wnt/β-catenin, hedgehog, Notch and PI3K pathways on GSK-3 activity-Diverse effects on cell growth, metabolism and cancer

Giuseppe Montalto, Li V Yang, Melchiorre Cervello, Alberto M Martelli, Concettina Fenga, Timothy L Fitzgerald, Ferdinando Nicoletti, Steve L Abrams, Agnieszka Gizak, Kvin Lertpiriyapong, Aurora Scalisi, Dariusz Rakus, Sandra Marmiroli, Massimo Libra, Linda S Steelman, James A Mccubrey, Luca M Neri, Lucio Cocco, Giuseppe Montalto, Steve L AbramsFrancesco Torino

Risultato della ricerca: Articlepeer review

78 Citazioni (Scopus)

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.
Lingua originaleEnglish
pagine (da-a)2942-2976
Numero di pagine35
RivistaBIOCHIMICA ET BIOPHYSICA ACTA. MOLECULAR CELL RESEARCH
Volume1863
Stato di pubblicazionePublished - 2016

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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