C-Myc uses Cul4b to preserve genome integrity and promote antiviral CD8⁺ T cell immunity.

ABSTRACT: During infection, virus-specific CD8⁺ T cells undergo rapid bursts of proliferation and differentiate into effector cells that kill virus-infected cells and reduce viral load. This rapid clonal expansion can put T cells at significant risk for replication-induced DNA damage. Here, we find that c-Myc links CD8⁺ T cell expansion to DNA damage response pathways though the E3 ubiquitin ligase, Cullin 4b (Cul4b). Following activation, c-Myc increases the levels of Cul4b and other members of the Cullin RING Ligase 4 (CRL4) complex. Despite expressing c-Myc at high levels, Cul4b-deficient CD8⁺ T cells do not expand and clear the Armstrong strain of lymphocytic choriomeningitis virus (LCMV) in vivo. Cul4b-deficient CD8⁺ T cells accrue DNA damage and succ

SUBMITTER: Dar AA 

PROVIDER: S-EPMC10625626 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature