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Unfolded p53 in the pathogenesis of Alzheimer's disease: is HIPK2 the link?

p53 transcriptional activity depends mainly on posttranslational modifications and protein/protein interaction. Another important mechanism that controls p53 function is its conformational stability since p53 is an intrinsically unstable protein. An altered conformational state of p53, independent f...

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Autores principales: Stanga, Serena, Lanni, Cristina, Govoni, Stefano, Uberti, Daniela, D'Orazi, Gabriella, Racchi, Marco
Formato: Texto
Lenguaje:English
Publicado: Impact Journals LLC 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2984604/
https://www.ncbi.nlm.nih.gov/pubmed/20876941
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author Stanga, Serena
Lanni, Cristina
Govoni, Stefano
Uberti, Daniela
D'Orazi, Gabriella
Racchi, Marco
author_facet Stanga, Serena
Lanni, Cristina
Govoni, Stefano
Uberti, Daniela
D'Orazi, Gabriella
Racchi, Marco
author_sort Stanga, Serena
collection PubMed
description p53 transcriptional activity depends mainly on posttranslational modifications and protein/protein interaction. Another important mechanism that controls p53 function is its conformational stability since p53 is an intrinsically unstable protein. An altered conformational state of p53, independent from point mutations, has been reported in tissues from patients with Alzheimer's disease (AD), leading to an impaired and dysfunctional response to stressors. Recent evidence shows that one of the activators that induces p53 posttranslational modification and wild-type conformational stability is homeodomain interacting protein kinase 2 (HIPK2). Hence, conditions that induce HIPK2 deregulation would result in a dysfunctional response to stressors by affecting p53 activity. Discovering the mechanisms of HIPK2 activation/inhibition and the ways to manipulate HIPK2 activity are an interesting option to affect several biological pathways, including those underlying AD. Soluble beta-amyloid peptides have recently been involved in HIPK2 degradation, in turn regulating the p53 conformational state and vulnerability to a noxious stimulus, before triggering the amyloidogenic cascade. Here we discuss about these findings and the potential relevance of HIPK2 as a target for AD and highlight the existence of a novel amyloid-based mechanism in AD potentially leading to the survival of injured dysfunctional cells.
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spelling pubmed-29846042010-11-18 Unfolded p53 in the pathogenesis of Alzheimer's disease: is HIPK2 the link? Stanga, Serena Lanni, Cristina Govoni, Stefano Uberti, Daniela D'Orazi, Gabriella Racchi, Marco Aging (Albany NY) Review p53 transcriptional activity depends mainly on posttranslational modifications and protein/protein interaction. Another important mechanism that controls p53 function is its conformational stability since p53 is an intrinsically unstable protein. An altered conformational state of p53, independent from point mutations, has been reported in tissues from patients with Alzheimer's disease (AD), leading to an impaired and dysfunctional response to stressors. Recent evidence shows that one of the activators that induces p53 posttranslational modification and wild-type conformational stability is homeodomain interacting protein kinase 2 (HIPK2). Hence, conditions that induce HIPK2 deregulation would result in a dysfunctional response to stressors by affecting p53 activity. Discovering the mechanisms of HIPK2 activation/inhibition and the ways to manipulate HIPK2 activity are an interesting option to affect several biological pathways, including those underlying AD. Soluble beta-amyloid peptides have recently been involved in HIPK2 degradation, in turn regulating the p53 conformational state and vulnerability to a noxious stimulus, before triggering the amyloidogenic cascade. Here we discuss about these findings and the potential relevance of HIPK2 as a target for AD and highlight the existence of a novel amyloid-based mechanism in AD potentially leading to the survival of injured dysfunctional cells. Impact Journals LLC 2010-09-22 /pmc/articles/PMC2984604/ /pubmed/20876941 Text en Copyright: © 2010 Stanga et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
spellingShingle Review
Stanga, Serena
Lanni, Cristina
Govoni, Stefano
Uberti, Daniela
D'Orazi, Gabriella
Racchi, Marco
Unfolded p53 in the pathogenesis of Alzheimer's disease: is HIPK2 the link?
title Unfolded p53 in the pathogenesis of Alzheimer's disease: is HIPK2 the link?
title_full Unfolded p53 in the pathogenesis of Alzheimer's disease: is HIPK2 the link?
title_fullStr Unfolded p53 in the pathogenesis of Alzheimer's disease: is HIPK2 the link?
title_full_unstemmed Unfolded p53 in the pathogenesis of Alzheimer's disease: is HIPK2 the link?
title_short Unfolded p53 in the pathogenesis of Alzheimer's disease: is HIPK2 the link?
title_sort unfolded p53 in the pathogenesis of alzheimer's disease: is hipk2 the link?
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2984604/
https://www.ncbi.nlm.nih.gov/pubmed/20876941
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