The GCN2/eIF2αK stress kinase regulates PP1 to ensure mitotic fidelity

ABSTRACT: GCN2/eIF2αK4 is exclusively seen as an eIF2α kinase, which regulates reprogramming of protein translation in response to stress. Here we show that GCN2 has an unexpected role in unstressed cells as a regulator of mitosis. This function is not through its canonical role in translation reprogramming, but through regulation of two previously unidentified substrates, PP1α and γ. In the absence of GCN2 function, timing and levels of phosphorylation of key mitotic players are altered, leading to aberrant chromosome alignment, missegregating chromosomes, elevated number of tripolar spindles, and a delay in progression through mitosis. Pharmacological inhibition of GCN2 results in similar effects and is synergistic with Aurora A inhibition in causing more severe mitotic errors and cell death. We s

SUBMITTER: Dr. Vilte Stonyte 

PROVIDER: S-SCDT-10_15252-EMBR_202256100 | biostudies-other |

REPOSITORIES: biostudies-other