Cargando…
Multifaceted Roles of GSK-3 in Cancer and Autophagy-Related Diseases
GSK-3 is a ubiquitously expressed serine/threonine kinase existing as GSK-3α and GSK-3β isoforms, both active under basal conditions and inactivated upon phosphorylation by different upstream kinases. Initially discovered as a regulator of glycogen synthesis, GSK-3 is also involved in several signal...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5742885/ https://www.ncbi.nlm.nih.gov/pubmed/29379583 http://dx.doi.org/10.1155/2017/4629495 |
_version_ | 1783288472247730176 |
---|---|
author | Mancinelli, Romina Carpino, Guido Petrungaro, Simonetta Mammola, Caterina Loredana Tomaipitinca, Luana Filippini, Antonio Facchiano, Antonio Ziparo, Elio Giampietri, Claudia |
author_facet | Mancinelli, Romina Carpino, Guido Petrungaro, Simonetta Mammola, Caterina Loredana Tomaipitinca, Luana Filippini, Antonio Facchiano, Antonio Ziparo, Elio Giampietri, Claudia |
author_sort | Mancinelli, Romina |
collection | PubMed |
description | GSK-3 is a ubiquitously expressed serine/threonine kinase existing as GSK-3α and GSK-3β isoforms, both active under basal conditions and inactivated upon phosphorylation by different upstream kinases. Initially discovered as a regulator of glycogen synthesis, GSK-3 is also involved in several signaling pathways controlling many different key functions. Here, we discuss recent advances regarding (i) GSK-3 structure, function, regulation, and involvement in several cancers, including hepatocarcinoma, cholangiocarcinoma, breast cancer, prostate cancer, leukemia, and melanoma (active GSK-3 has been shown to induce apoptosis in some cases or inhibit apoptosis in other cases and to induce cancer progression or inhibit tumor cell proliferation, suggesting that different GSK-3 modulators may address different specific targets); (ii) GSK-3 involvement in autophagy modulation, reviewing signaling pathways involved in neurodegenerative and liver diseases; (iii) GSK-3 role in oxidative stress and autophagic cell death, focusing on liver injury; (iv) GSK-3 as a possible therapeutic target of natural substances and synthetic inhibitors in many diseases; and (v) GSK-3 role as modulator of mammalian aging, related to metabolic alterations characterizing senescent cells and age-related diseases. Studies summarized here underline the GSK-3 multifaceted role and indicate such kinase as a molecular target in different pathologies, including diseases associated with autophagy dysregulation. |
format | Online Article Text |
id | pubmed-5742885 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-57428852018-01-29 Multifaceted Roles of GSK-3 in Cancer and Autophagy-Related Diseases Mancinelli, Romina Carpino, Guido Petrungaro, Simonetta Mammola, Caterina Loredana Tomaipitinca, Luana Filippini, Antonio Facchiano, Antonio Ziparo, Elio Giampietri, Claudia Oxid Med Cell Longev Review Article GSK-3 is a ubiquitously expressed serine/threonine kinase existing as GSK-3α and GSK-3β isoforms, both active under basal conditions and inactivated upon phosphorylation by different upstream kinases. Initially discovered as a regulator of glycogen synthesis, GSK-3 is also involved in several signaling pathways controlling many different key functions. Here, we discuss recent advances regarding (i) GSK-3 structure, function, regulation, and involvement in several cancers, including hepatocarcinoma, cholangiocarcinoma, breast cancer, prostate cancer, leukemia, and melanoma (active GSK-3 has been shown to induce apoptosis in some cases or inhibit apoptosis in other cases and to induce cancer progression or inhibit tumor cell proliferation, suggesting that different GSK-3 modulators may address different specific targets); (ii) GSK-3 involvement in autophagy modulation, reviewing signaling pathways involved in neurodegenerative and liver diseases; (iii) GSK-3 role in oxidative stress and autophagic cell death, focusing on liver injury; (iv) GSK-3 as a possible therapeutic target of natural substances and synthetic inhibitors in many diseases; and (v) GSK-3 role as modulator of mammalian aging, related to metabolic alterations characterizing senescent cells and age-related diseases. Studies summarized here underline the GSK-3 multifaceted role and indicate such kinase as a molecular target in different pathologies, including diseases associated with autophagy dysregulation. Hindawi 2017 2017-12-12 /pmc/articles/PMC5742885/ /pubmed/29379583 http://dx.doi.org/10.1155/2017/4629495 Text en Copyright © 2017 Romina Mancinelli et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Review Article Mancinelli, Romina Carpino, Guido Petrungaro, Simonetta Mammola, Caterina Loredana Tomaipitinca, Luana Filippini, Antonio Facchiano, Antonio Ziparo, Elio Giampietri, Claudia Multifaceted Roles of GSK-3 in Cancer and Autophagy-Related Diseases |
title | Multifaceted Roles of GSK-3 in Cancer and Autophagy-Related Diseases |
title_full | Multifaceted Roles of GSK-3 in Cancer and Autophagy-Related Diseases |
title_fullStr | Multifaceted Roles of GSK-3 in Cancer and Autophagy-Related Diseases |
title_full_unstemmed | Multifaceted Roles of GSK-3 in Cancer and Autophagy-Related Diseases |
title_short | Multifaceted Roles of GSK-3 in Cancer and Autophagy-Related Diseases |
title_sort | multifaceted roles of gsk-3 in cancer and autophagy-related diseases |
topic | Review Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5742885/ https://www.ncbi.nlm.nih.gov/pubmed/29379583 http://dx.doi.org/10.1155/2017/4629495 |
work_keys_str_mv | AT mancinelliromina multifacetedrolesofgsk3incancerandautophagyrelateddiseases AT carpinoguido multifacetedrolesofgsk3incancerandautophagyrelateddiseases AT petrungarosimonetta multifacetedrolesofgsk3incancerandautophagyrelateddiseases AT mammolacaterinaloredana multifacetedrolesofgsk3incancerandautophagyrelateddiseases AT tomaipitincaluana multifacetedrolesofgsk3incancerandautophagyrelateddiseases AT filippiniantonio multifacetedrolesofgsk3incancerandautophagyrelateddiseases AT facchianoantonio multifacetedrolesofgsk3incancerandautophagyrelateddiseases AT ziparoelio multifacetedrolesofgsk3incancerandautophagyrelateddiseases AT giampietriclaudia multifacetedrolesofgsk3incancerandautophagyrelateddiseases |