| Title: | The histone H2B Arg95 residue links the pheromone response pathway to rapamycin-induced G(1) arrest in yeast |
| Author(s): | Alhaj Sulaiman A; Ali R; Aouida M; Moovarkumudalvan B; Ramotar D; |
| Address: | "Division of Biological and Biomedical Sciences, College of Health and Life Sciences, Hamad Bin Khalifa University, Education City, Qatar Foundation, P.O. Box: 34110, Doha, Qatar. Division of Biological and Biomedical Sciences, College of Health and Life Sciences, Hamad Bin Khalifa University, Education City, Qatar Foundation, P.O. Box: 34110, Doha, Qatar. dramotar@hbku.edu.qa" |
| DOI: | 10.1038/s41598-022-14053-9 |
| ISSN/ISBN: | 2045-2322 (Electronic) 2045-2322 (Linking) |
| Abstract: | "Rapamycin is an immunosuppressant used for treating many types of diseases such as kidney carcinomas. In yeast, rapamycin inhibits the TORC1 kinase signaling pathway causing rapid alteration in gene expression and ultimately cell cycle arrest in G(1) through mechanisms that are not fully understood. Herein, we screened a histone mutant collection and report that one of the mutants, H2B R95A, is strikingly resistant to rapamycin due to a defective cell cycle arrest. We show that the H2B R95A causes defects in the expression of a subset of genes of the pheromone pathway required for alpha factor-induced G(1) arrest. The expression of the STE5 gene and its encoded scaffold protein Ste5, required for the sequential activation of the MAPKs of the pheromone pathway, is greatly reduced in the H2B R95A mutant. Similar to the H2B R95A mutant, cells devoid of Ste5 are also resistant to rapamycin. Rapamycin-induced G(1) arrest does not involve detectable phosphorylation of the MAPKs, Kss1, and Fus3, as reported for alpha factor-induced G(1) arrest. However, we observed a sharp induction of the G(1) cyclin Cln2 (~ 3- to 4-fold) in the ste5Delta mutant within 30 min of exposure to rapamycin. Our data provide a new insight whereby rapamycin signaling via the Torc1 kinase may exploit the pheromone pathway to arrest cells in the G(1) phase" |
| Keywords: | "Adaptor Proteins, Signal Transducing/metabolism Cyclins/metabolism Fungal Proteins/genetics Histones/metabolism Mechanistic Target of Rapamycin Complex 1/metabolism Mitogen-Activated Protein Kinases/metabolism Pheromones/metabolism *Saccharomyces cerevisi;" |
| Notes: | "MedlineAlhaj Sulaiman, Abdallah Ali, Reem Aouida, Mustapha Moovarkumudalvan, Balasubramanian Ramotar, Dindial eng Research Support, Non-U.S. Gov't England 2022/06/16 Sci Rep. 2022 Jun 15; 12(1):10023. doi: 10.1038/s41598-022-14053-9" |
