ATM kinase: Much more than a DNA damage responsive protein

Area of Science:

• Molecular Biology
• Cellular Biology
• Biochemistry

Background:

• ATM (ataxia-telangiectasia mutated) is a crucial protein kinase with diverse cellular functions.
• Beyond its established role in DNA damage response, ATM is vital for maintaining overall cellular integrity.
• ATM mutations or deficiency lead to pathological conditions including oxidative stress, metabolic syndrome, mitochondrial dysfunction, and neurodegeneration.

Purpose of the Study:

• To review the multifaceted roles of ATM in various pathophysiological conditions.
• To consolidate current understanding of ATM's involvement in DNA damage and non-DNA damage pathways.
• To highlight the therapeutic potential of understanding ATM-mediated signaling.

Main Methods:

• Comprehensive literature review of studies on ATM.
• Analysis of high-throughput screening data (proteomics, metabolomics, transcriptomics) identifying ATM substrates.
• Synthesis of information on ATM's involvement in diverse cellular processes.

Main Results:

• ATM plays a central role in DNA damage response and maintaining cellular homeostasis.
• ATM dysfunction is implicated in a spectrum of diseases, including neurodegeneration and metabolic disorders.
• Recent studies have identified novel ATM substrates and pathways, offering insights into its regulation.

Conclusions:

• A deeper understanding of ATM-dependent cellular signals is crucial for developing novel therapeutics.
• Targeting ATM pathways may offer treatment strategies for a wider range of diseases beyond Ataxia-Telangiectasia.
• ATM's extensive involvement in critical cellular functions underscores its significance in health and disease.