Proteomic profiling of ATM kinase proficient and deficient cell lines upon blockage of proteasome activity.
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.
Proteomic and Metabonomic Laboratory, Fondazione Santa Lucia, 00143 Rome, Italy.
Valeria
V
Marzano
Simonetta
S
Santini
Claudia
C
Rossi
Mirco
M
Zucchelli
Annamaria
A
D'Alessandro
Carlo
C
Marchetti
Michele
M
Mingardi
Venturina
V
Stagni
Daniela
D
Barilà
Andrea
A
Urbani
D001260:Ataxia Telangiectasia / Q000378:metabolism*; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D006019:Glycolysis; D006367:HeLa Cells; D006801:Humans; D046988:Proteasome Endopeptidase Complex; D061988:Proteasome Inhibitors / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases; D055550:Protein Stability; D020543:Proteome / Q000378:metabolism*; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D061988:Proteasome Inhibitors; D020543:Proteome; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; D046988:Proteasome Endopeptidase Complex