| First Author | Yan Q | Year | 2022 |
| Journal | Front Cell Dev Biol | Volume | 10 |
| Pages | 728771 | PubMed ID | 35281086 |
| Mgi Jnum | J:321976 | Mgi Id | MGI:7255281 |
| Doi | 10.3389/fcell.2022.728771 | Citation | Yan Q, et al. (2022) CTLA-4 Facilitates DNA Damage-Induced Apoptosis by Interacting With PP2A. Front Cell Dev Biol 10:728771 |
| abstractText | Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) plays a pivotal role in regulating immune responses. It accumulates in intracellular compartments, translocates to the cell surface, and is rapidly internalized. However, the cytoplasmic function of CTLA-4 remains largely unknown. Here, we describe the role of CTLA-4 as an immunomodulator in the DNA damage response to genotoxic stress. Using isogenic models of murine T cells with either sufficient or deficient CTLA-4 expression and performing a variety of assays, including cell apoptosis, cell cycle, comet, western blotting, co-immunoprecipitation, and immunofluorescence staining analyses, we show that CTLA-4 activates ataxia-telangiectasia mutated (ATM) by binding to the ATM inhibitor protein phosphatase 2A into the cytoplasm of T cells following transient treatment with zeocin, exacerbating the DNA damage response and inducing apoptosis. These findings provide new insights into how T cells maintain their immune function under high-stress conditions, which is clinically important for patients with tumors undergoing immunotherapy combined with chemoradiotherapy. |
