Cellular stress induces cap-independent alpha-enolase/MBP-1 translation

• MBP-1 arises through the alternative translation of the mRNA encoding alpha-enolase.
• Cellular response to stressful conditions may activate cap-independent translation.
• A stress-mediated regulatory mechanism of MPB-1 expression is proposed.
• Glycolysis inhibition and ER stress induction lead to MPB-1 expression.
• Inhibition or silencing of signalling actors explain the committed mechanisms.

Myc promoter-binding protein-1 (MBP-1) is a shorter protein variant of the glycolytic enzyme alpha-enolase. Although several lines of evidence indicate that MBP-1 acts as a tumor suppressor, the cellular mechanisms and signaling pathways underlying MBP-1 expression still remain largely elusive. To dissect these pathways, we used the SkBr3 breast cancer cell line and non-tumorigenic HEK293T cells ectopically overexpressing alpha-enolase/MBP-1. Here, we demonstrate that induced cell stresses promote MBP-1 expression through the AKT/PERK/eIF2α signaling axis. Our results contribute to shedding light on the molecular mechanisms underlying MBP-1 expression in non-tumorigenic and cancer cells.