Stonyte, V. | Search bioRxiv

bioRxiv2025

Analysis of patient data reveals novel cancer-relevant functions for GCN2/eIF2αK4

Numerous studies have shown that high GCN2 levels correlate with poor survival in a number of cancers. GCN2 has been known for over thirty years as a stress-response kinase, which phosphorylates the translation-initiation factor eIF2, and thereby contributes to reprogramming of translation. Here we performed correlation analyses of GCN2 expression and that of other genes in a patient-derived sample set of cervical cancer samples. We found correlations not only with genes involved in stress responses, but also with genes involved in mitosis and cell migration. Our functional analyses confirmed that these correlations indeed reveal novel functions. Furthermore, our analyses of growth benefits associated with elevated GCN2 levels suggest that the novel functions can contribute to aggressive disease in cancers with high GCN2 levels.

cell biology↗

bioRxiv2018

Regulation of global translation during the cell cycle

It is generally accepted that global translation varies during the cell cycle and is low in mitosis. However, addressing this issue is challenging because it involves cell synchronization, which evokes stress responses which, in turn, affect translation rates. Here we have used two approaches to measure global translation rates in different cell-cycle phases. First, synchrony in different cell-cycle phases was obtained involving the same stress, by using temperature-sensitive mutants. Second, translation and DNA content were measured by flow cytometry in exponentially growing, single cells. We found no major variation in global translation rates through the cell cycle in either fission-yeast or mammalian cells. We also measured phosphorylation of eukaryotic initiation factor-2, an event thought to downregulate global translation in mitosis. In contrast with the prevailing view, eIF2 phosphorylation correlated poorly with downregulation of general translation and ectopically induced eIF2 phosphorylation inhibited general translation only at high levels.

cell biology↗