AUTHOR=Yan Qiongyu , Zhang Bin , Ling Xi , Zhu Bin , Mei Shenghui , Yang Hua , Zhang Dongjie , Huo Jiping , Zhao Zhigang 

TITLE=CTLA-4 Facilitates DNA Damage–Induced Apoptosis by Interacting With PP2A

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=Volume 10 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2022.728771

DOI=10.3389/fcell.2022.728771

ISSN=2296-634X

ABSTRACT=T lymphocytes are constantly exposed to endogenous and extracellular stress that likely lead to many types of damage to DNA. Maintaining genome stability is critical for faithful genome inheritance and prevention of mutagenesis. CTLA-4 is an inhibitory molecule found on T cells. They accumulate in the intracellular compartment, travel to the cell surface and rapidly internalize. However, the cytoplasmic function of CTLA-4 remains largely unknown. Here, we found that upon DNA damage, cytoplasmic of CTLA4 activated ATM by sequestering the ATM inhibitor PP2A into cytoplasm, further activating downstream targets, arresting cell cycle at the G2/M phase, and inducing cell apoptosis. This report showed the importance of CTLA-4 for the maintaining the stability of the genome and its molecular mechanisms.