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Detection and Visualization of DNA Damage-induced Protein Complexes in Suspension Cell Cultures Using the Proximity Ligation Assay
Published on: June 9, 2017
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CTLA-4 Facilitates DNA Damage-Induced Apoptosis by Interacting With PP2A
Qiongyu Yan1, Bin Zhang2, Xi Ling1
1Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Frontiers in Cell and Developmental Biology
|March 14, 2022
Summary
Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) regulates immune responses by modulating the DNA damage response. CTLA-4 activation of ATM exacerbates DNA damage and induces T cell apoptosis under genotoxic stress.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is a key regulator of immune responses.
- Its intracellular functions, particularly in response to DNA damage, are not well understood.
Purpose of the Study:
- To investigate the cytoplasmic role of CTLA-4 in the DNA damage response of T cells.
- To elucidate the mechanism by which CTLA-4 influences genotoxic stress response.
Main Methods:
- Utilized isogenic murine T cell models with varying CTLA-4 expression.
- Employed assays including apoptosis, cell cycle, comet assay, western blotting, co-immunoprecipitation, and immunofluorescence staining.
Main Results:
- CTLA-4 was found to activate ataxia-telangiectasia mutated (ATM) signaling.
- This activation occurs through CTLA-4 binding to protein phosphatase 2A in the cytoplasm.
- CTLA-4 exacerbates DNA damage response and induces apoptosis following genotoxic stress.
Conclusions:
- CTLA-4 acts as an cytoplasmic immunomodulator in the DNA damage response.
- These findings offer novel insights into T cell immune function maintenance under stress.
- Clinically relevant for cancer immunotherapy combined with chemoradiotherapy.
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