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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.<\/jats:p>","DOI":"10.1242\/jcs.264507","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T08:00:06Z","timestamp":1776844806000},"source":"Crossref","is-referenced-by-count":0,"title":["Temperature-specific regulation of the NDR kinase Orb6 by the MAPK Sty1 to promote heat stress resilience"],"prefix":"10.1242","volume":"139","author":[{"given":"Laura P.","family":"Doyle","sequence":"first","affiliation":[{"name":"University of Miami Department of Molecular and Cellular Pharmacology , , Miami, FL ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert N.","family":"Tams","sequence":"additional","affiliation":[{"name":"University of Miami Department of Molecular and Cellular Pharmacology , , Miami, FL ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chuan","family":"Chen","sequence":"additional","affiliation":[{"name":"University of Miami Department of Molecular and Cellular Pharmacology , , Miami, FL ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Illyce","family":"Nu\u00f1ez","sequence":"additional","affiliation":[{"name":"University of Miami Department of Molecular and Cellular Pharmacology , , Miami, FL ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick Roman","family":"Haller","sequence":"additional","affiliation":[{"name":"University of Miami Department of Molecular and Cellular Pharmacology , , Miami, FL ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2575-0823","authenticated-orcid":false,"given":"Fulvia","family":"Verde","sequence":"additional","affiliation":[{"name":"University of Miami Department of Molecular and Cellular Pharmacology , , Miami, FL ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2026,4,22]]},"reference":[{"key":"2026042204000028500_JCS264507C1","first-page":"3788","article-title":"Analysis of gene expression in ductal carcinoma in situ of the breast","volume":"8","author":"Adeyinka","year":"2002","journal-title":"Clin. 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