RSK2-mediated cGAS phosphorylation induces cGAS chromatin-incorporation-mediated cell transformation and cancer cell colony growth.

ABSTRACT: Cyclic guanosine-adenosine monophosphate synthase (cGAS) is a key cytosolic DNA sensor that plays a pivotal role in the innate immune response. Although a decade of research on the cGAS has advanced our understanding of inflammasome formation, cytokine production, and signaling pathways, the role of cGAS in the nucleus remains unclear. In this study, we found that the nuclear localization of endogenous and stably expressed cGAS differed from transiently expressed cGAS, which mainly localized in the cytosol. In the nucleus, cGAS is tightly bound to chromatin DNA. The chromatin DNA binding of cGAS was dependent on RSK2. Our molecular mechanism study indicated that the N-lobe of RSK2 harboring 1-323 interacted with the NTase domain of cGAS harboring residues 213-330. This interaction increase

SUBMITTER: Chen W 

PROVIDER: S-EPMC11492232 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature