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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)4632-4646
Number of pages15
JournalJournal of Proteomics
Volume75
Issue number15
DOIs
Publication statusPublished - Aug 3 2012

Keywords

  • ATM kinase
  • Carbohydrate metabolism
  • Proteasome
  • Shotgun

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics

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