This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: A new study from Ben-Gurion University of the Negev (BGU) has identified a molecular switch that controls whether stressed human cells activate a survival mechanism or trigger programmed cell death (apoptosis). The findings, published in Redox Biology, provide insights that could help overcome chemotherapy resistance in aggressive tumors.
Aeid Igbaria alongside co-lead authors Laila Abu Madegam and Noa Gavriel and researcher Raifu Tolulope Adebisi, all from BGU's Department of Life Sciences. The endoplasmic reticulum (ER) serves as the cell's primary protein production and folding center. When subjected to physiological stress, the ER relieves internal pressure through an adaptive process known as ER-to-cytosol signaling (ERCYS).
Through this pathway, select proteins escape the ER into the surrounding cytosol, where they acquire protective functions that block tumor suppressors and deactivate cell-death enzymes such as caspase-3 and wt-p53. While cancer cells frequently hijack this pathway to survive harsh microenvironments and resist drug treatments, the molecular mechanism governing when this escape route operates—and why it shuts down under extreme stress—has long remained unclear. Using pharmacological and physiological stress models across multiple human cell lines, the BGU research team discovered that this survival mechanism operates within a tightly defined stress window controlled by the cell's chemical reduction-oxidation (redox) balance: "Our findings demonstrate that the cell's internal redox balance functions as a definitive molecular scale," explains Igbaria.
"Instead of a passive structural breakdown, the cell actively measures stress levels through the integrity of these chemical bonds. Under manageable stress, it deploys molecular chaperones to survive, but when the stress threshold is breached, it systematically dismantles those protectors to execute cell death." "Understanding how this switch is flipped gives us a clear therapeutic target," adds co-lead author Abu Madegam. "Because cancer cells rely heavily on this chaperone-assisted pathway to resist chemotherapy, disrupting DNAJB12 and DNAJB14 or altering the ER redox environment could strip tumor cells of their defenses and force them into apoptosis." The researchers also verified this molecular cascade in cardiac models of hypoxia-reoxygenation, indicating that modulating this switch could offer new strategies to protect heart muscle from massive cell death following ischemic injury.
Laila Abu Madegam et al, DNAJB12/14 redox switching directs chaperone- and Bax/Bak-dependent ER protein reflux, Redox Biology (2026). DOI: 10.1016/j.redox.2026.104324 Provided by Ben-Gurion University of the Negev MA in English, copy editor since 2021 with experience in higher education and health content. Dedicated to trustworthy science news.
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