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Genetic Profiling and Genome-Scale Dropout Screening to Identify Therapeutic Targets in Mouse Models of Malignant Peripheral Nerve Sheath Tumor
Published on: August 25, 2023
Genomic and proteomic screening of apoptosis mitochondrial regulators for drug target discovery
Gael Lecellier1, Catherine Brenner
1Université de Versailles/SQY, CNRS UMR8159, 45 avenue des Etats-Unis, 78035 Versailles, France.
Abstract:
Screening strategies of therapeutic molecules and targets have received increasing attention during the past few years. Indeed, identification of novel compounds and drug targets involved in apoptosis control is a major rate-limiting step in anticancer drug development efforts. In this review, we discuss the current screening methodologies to discover novel potential therapeutics targets and drugs implicated in the apoptotic pathway, in particular the intrinsic pathway. In addition, we present a proteomic screening strategy that led us to identify a mitochondrial glutathione-S-transferase as a novel regulator of the pro-apoptotic adenine nucleotide translocase pore function.
Insights
Identifying new anticancer drugs and targets is crucial. This review covers screening methods for apoptosis regulators, highlighting a proteomic strategy that found a mitochondrial enzyme controlling cell death.
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- Apoptosis control is vital for anticancer drug development.
- Identifying novel therapeutic targets and compounds in apoptosis is a key challenge.
- The intrinsic apoptotic pathway is a significant focus for cancer research.
Purpose of the Study:
- To review current screening methodologies for discovering drugs and targets in apoptosis.
- To focus on screening strategies for the intrinsic apoptotic pathway.
- To present a proteomic approach for identifying novel apoptosis regulators.
Main Methods:
- Literature review of screening strategies for apoptosis targets.
- Proteomic screening approach.
- Analysis of mitochondrial glutathione-S-transferase and adenine nucleotide translocase interaction.
Main Results:
- A proteomic strategy successfully identified novel regulators of apoptosis.
- Mitochondrial glutathione-S-transferase was identified as a key regulator.
- This enzyme modulates the function of the pro-apoptotic adenine nucleotide translocase pore.
Conclusions:
- Proteomic screening is effective for discovering apoptosis regulators.
- Mitochondrial glutathione-S-transferase represents a potential therapeutic target for cancer.
- Understanding these regulatory mechanisms can advance anticancer drug development.
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