Temperature-specific regulation of the NDR kinase Orb6 by the MAPK Sty1 to promote heat stress resilience
Year: 2026
Type: article
Abstract: The cellular response to environmental fluctuations, such as increased temperature, is crucial in promoting cell survival and plays an increasingly recognized role in cancer biology. Important cellular functions altered by heat stress are cell polarization and protein translation. Previous studies have shown that heat stress alters the dynamics of Cdc42, a key regulator of cell polarization in eukaryotes, and promotes ribonucleoprotein (RNP) granule formation, reprogramming protein translation. The biological mechanisms underlying these vast changes are only partially known. Here, we report that the conserved NDR kinase Orb6, a homolog of mammalian STK38, responds to heat stress and regulates heat stress resilience by modulating Cdc42 dynamics and promoting RNP granule assembly in Schizosaccharomyces pombe. Also, we discovered a finely tuned mechanism whereby stress-activated mitogen-activated protein kinase (MAPK) Sty1 negatively regulates Orb6 kinase and Orb6 C-terminal phosphorylation during heat stress. Orb6 inhibition by Sty1 increases the sensitivity of the cell to heat stress in a temperature-specific manner, fostering increased stress resilience and metabolic adaptation. These observations highlight the role of NDR kinase in the process of heat adaptation and thermotolerance during environmental cell exposure to elevated temperatures.
Source: Journal of Cell Science
DOI: 10.1242/jcs.264507
Institution: University of Miami
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Awards: G9000016342, G9000038791
OpenAlex ID: W7155218269