Maintenance of p-eIF2alpha levels by the eIF2B complex is vital for colorectal cancer

ABSTRACT: Protein synthesis is an essential process, deregulated in multiple tumor types showing differential dependence on translation factors compared to untransformed tissue. We show that colorectal cancer (CRC) with loss-of-function mutation in the APC tumor suppressor depends on an oncogenic translation program regulated by the ability to sense phosphorylated eIF2a (p-eIF2a). Despite increased protein synthesis rates following APC loss, eIF2a phosphorylation, typically associated with translation inhibition, is enhanced in CRC. Elevated p-eIF2a, and its proper sensing by the decameric eIF2B complex, are essential to balance translation. Knockdown or mutation of eIF2Ba and eIF2Bd, two eIF2B subunits responsible for sensing p-eIF2a, impairs CRC viability, demonstrating that the eIF2B/p-eIF2a nexu

SUBMITTER: Ivana Paskov Skapik 

PROVIDER: S-SCDT-10_1038-S44318-025-00381-9 | biostudies-other |

REPOSITORIES: biostudies-other