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The p53 mRNA: an integral part of the cellular stress response.
Haronikova, Lucia; Olivares-Illana, Vanesa; Wang, Lixiao; Karakostis, Konstantinos; Chen, Sa; Fåhraeus, Robin.
Afiliação
  • Haronikova L; RECAMO, Masaryk Memorial Cancer Institute, Zluty kopec 7, 656 53 Brno, Czech Republic.
  • Olivares-Illana V; Laboratorio de Interacciones Biomoleculares y cáncer. Instituto de Física Universidad Autónoma de San Luis Potosí, Manuel Nava 6, Zona universitaria, 78290 SLP, México.
  • Wang L; Department of Medical Biosciences, Umeå University, 90185 Umeå, Sweden.
  • Karakostis K; Inserm U1162, 27 rue Juliette Dodu, 75010 Paris, France.
  • Chen S; Department of Medical Biosciences, Umeå University, 90185 Umeå, Sweden.
  • Fåhraeus R; RECAMO, Masaryk Memorial Cancer Institute, Zluty kopec 7, 656 53 Brno, Czech Republic.
Nucleic Acids Res ; 47(7): 3257-3271, 2019 04 23.
Article em En | MEDLINE | ID: mdl-30828720
ABSTRACT
A large number of signalling pathways converge on p53 to induce different cellular stress responses that aim to promote cell cycle arrest and repair or, if the damage is too severe, to induce irreversible senescence or apoptosis. The differentiation of p53 activity towards specific cellular outcomes is tightly regulated via a hierarchical order of post-translational modifications and regulated protein-protein interactions. The mechanisms governing these processes provide a model for how cells optimize the genetic information for maximal diversity. The p53 mRNA also plays a role in this process and this review aims to illustrate how protein and RNA interactions throughout the p53 mRNA in response to different signalling pathways control RNA stability, translation efficiency or alternative initiation of translation. We also describe how a p53 mRNA platform shows riboswitch-like features and controls the rate of p53 synthesis, protein stability and modifications of the nascent p53 protein. A single cancer-derived synonymous mutation disrupts the folding of this platform and prevents p53 activation following DNA damage. The role of the p53 mRNA as a target for signalling pathways illustrates how mRNA sequences have co-evolved with the function of the encoded protein and sheds new light on the information hidden within mRNAs.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Estresse Fisiológico / RNA Mensageiro / Proteína Supressora de Tumor p53 Limite: Animals / Humans Idioma: En Revista: Nucleic Acids Res Ano de publicação: 2019 Tipo de documento: Article País de afiliação: República Tcheca

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Estresse Fisiológico / RNA Mensageiro / Proteína Supressora de Tumor p53 Limite: Animals / Humans Idioma: En Revista: Nucleic Acids Res Ano de publicação: 2019 Tipo de documento: Article País de afiliação: República Tcheca