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The histone H2B Arg95 residue links the pheromone response pathway to rapamycin-induced G1 arrest in yeast

journal contribution
submitted on 2024-04-16, 07:58 and posted on 2024-04-16, 07:59 authored by Abdallah Alhaj Sulaiman, Reem Ali, Mustapha Aouida, Balasubramanian Moovarkumudalvan, Dindial Ramotar

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 G1 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 α factor-induced G1 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 G1 arrest does not involve detectable phosphorylation of the MAPKs, Kss1, and Fus3, as reported for α factor-induced G1 arrest. However, we observed a sharp induction of the G1 cyclin Cln2 (~ 3- to 4-fold) in the ste5Δ 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 G1 phase.

Other Information

Published in: Scientific Reports
License: https://creativecommons.org/licenses/by/4.0
See article on publisher's website: https://dx.doi.org/10.1038/s41598-022-14053-9

History

Language

  • English

Publisher

Springer Nature

Publication Year

  • 2022

License statement

This Item is licensed under the Creative Commons Attribution 4.0 International License.

Institution affiliated with

  • Hamad Bin Khalifa University
  • College of Health and Life Sciences - HBKU

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