Scientists identify key role of p38-MK2 pathway in determining cell fate in stress response

Living organisms are often exposed to stress stimuli generated by external or internal factors, and they must react accordingly. At the cellular level, stress typically triggers the activation of survival pathways that help recover cell homeostasis. However, when the stress is too high, a process of cell death is triggered which eliminates the damaged cell.

Scientists led by ICREA researcher Dr Angel Nebreda, head of the Signaling and Cell Cycle Laboratory at IRB Barcelona, ​​have identified an important role of the p38-MK2 pathway in determining the fate of cells in response to stress.

Our study describes a molecular mechanism that cells can use to translate stress-induced activation of the p38a-MK2 pathway into an appropriate biological response. “

Dr. Angel Nebreda, Head of Signaling and Cell Cycle Laboratory at IRB Barcelona

When cells are exposed to high levels of stress, the p38-MK2 pathway is sustainably activated, promoting the degradation of the MK2 protein, which correlates with cell death. However, moderate stress levels only trigger temporary activation of the p38-MK2 pathway, which allows MK2 to re-accumulate and leads to cell survival. Thus, MK2 protein levels act as a molecular indicator that tells cells whether they should stay alive or self-destruct.

“Using human and murine cell lines treated with different stress stimuli, we have shown that MK2 expression levels are regulated by stress intensity and that they are essential for the viability of stressed cells,” explains Dr. Núria Gutiérrez-Prat, who started labor. and is the first co-author of the article, along with Dr Mónica Cubillos-Rojas and Dr Begoña Canovas.

p38, a protein linked to stress and cancer

p38 is a central protein that regulates many cellular processes by modulating the activity of a number of other proteins. Diseases such as cancer show alterations in the p38 pathway, and high activity levels of p38 are sometimes linked to a poor prognosis, for example in lung tumors. Additionally, deregulation of this p38-MK2 pathway has been linked to several human diseases, such as inflammatory disorders and cancer.

Further studies will examine whether regulation of the p38-MK2 pathway in response to strong or sustained stress functions as a common sensor for irreversible damage among cell types. The researchers will also study the possible relevance of these stress response mechanisms in the onset of disease and whether the stress response differs in pathological situations.