Research
Professor Antonis E. Koromilas – Lady Davis Institute for Medical Research, Jewish General Hospital, Montréal
QBCF Strategic Grants Program
Research Factsheet
PR. ANTONIS E. KOROMILAS
LADY DAVIS INSTITUTE FOR MEDICAL RESEARCH, JEWISH GENERAL HOSPITAL, MONTREAL
PROJECT TITLE
Characterization of elF2a kinases as novel targets of concogenic signaling in breast tumorigenesis with therapeutic potential
PRINCIPAL INVESTIGATOR Professor Antonis E. Koromilas
INSTITUTE Lady Davis Institute for Medical Research
TOTAL RESEARCH BUDGET $306 817
RESEARCH SUMMARY*:
Translation of mRNAs is essential for cell function. The significance of regulating mRNA translation in tumors has been highlighted by the ability of anti-cancer drugs to target the translation initiation process itself and signaling pathwhays leading to translation initiation.
An important mechanism of regulation of translation initiation involves the phosphorylation of translation initiation factor eIF2. Phosphorylation of the alpha subunit of eIF2 at serine 51 compromises protein synthesis and is mediated by a family of kinases that respond to distinct types of stress including virus infection (PKR), endoplasmic reticulum (ER) stress (PERK), nutrient deprivation (GCN2) or oxidative stress (HRI).
There is evidence for a link between eIF2alpha phosphorylation and breast tumorigenesis.
That is, the eIF2alpha phosphorylation pathway is compromised in human breast cancer cells. Moreover, disturbances in the homeostasis of the ER are often seen in breast tumors and activation of PERK is associated with inhibition of proliferation of mamrilary epithelium.
* This document is a non-scientific summary.
