Proteomic profiling of ATM kinase proficient and deficient cell lines upon blockage of proteasome activity

Andrea Urbani, Valeria Marzano, Simonetta Santini, Claudia Rossi, Mirco Zucchelli, Annamaria D'Alessandro, Carlo Marchetti, Michele Mingardi, Venturina Stagni, Daniela Barilà

Risultato della ricerca: Contributo in rivistaArticolo in rivista

15 Citazioni (Scopus)

Abstract

Ataxia Telangiectasia Mutated (ATM) protein kinase is a key effector in the modulation of the functionality of some important stress responses, including DNA damage and oxidative stress response, and its deficiency is the hallmark of Ataxia Telangiectasia (A-T), a rare genetic disorder. ATM modulates the activity of hundreds of target proteins, essential for the correct balance between proliferation and cell death. The aim of this study is to evaluate the phenotypic adaptation at the protein level both in basal condition and in presence of proteasome blockage in order to identify the molecules whose level and stability are modulated through ATM expression. We pursued a comparative analysis of ATM deficient and proficient lymphoblastoid cells by label-free shotgun proteomic experiments comparing the panel of proteins differentially expressed. Through a non-supervised comparative bioinformatic analysis these data provided an insight on the functional role of ATM deficiency in cellular carbohydrate metabolism's regulation. This hypothesis has been demonstrated by targeted metabolic fingerprint analysis SRM (Selected Reaction Monitoring) on specific thermodynamic checkpoints of glycolysis. This article is part of a Special Issue entitled: Translational Proteomics.
Lingua originaleEnglish
pagine (da-a)4632-4646
Numero di pagine15
RivistaJOURNAL OF PROTEOMICS
Volume75
DOI
Stato di pubblicazionePubblicato - 2012

Keywords

  • Ataxia Telangiectasia
  • Ataxia Telangiectasia Mutated Proteins
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Glycolysis
  • HeLa Cells
  • Humans
  • Proteasome Endopeptidase Complex
  • Proteasome Inhibitors
  • Protein Stability
  • Protein-Serine-Threonine Kinases
  • Proteome
  • Tumor Suppressor Proteins

Fingerprint

Entra nei temi di ricerca di 'Proteomic profiling of ATM kinase proficient and deficient cell lines upon blockage of proteasome activity'. Insieme formano una fingerprint unica.

Cita questo