The histone H2B Arg95 residue links the pheromone response pathway to rapamycin-induced G1 arrest in yeast
<div><p>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...
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2022
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| author | Abdallah Alhaj Sulaiman (18372912) |
| author2 | Reem Ali (9913494) Mustapha Aouida (417652) Balasubramanian Moovarkumudalvan (18300811) Dindial Ramotar (208416) |
| author2_role | author author author author |
| author_facet | Abdallah Alhaj Sulaiman (18372912) Reem Ali (9913494) Mustapha Aouida (417652) Balasubramanian Moovarkumudalvan (18300811) Dindial Ramotar (208416) |
| author_role | author |
| dc.creator.none.fl_str_mv | Abdallah Alhaj Sulaiman (18372912) Reem Ali (9913494) Mustapha Aouida (417652) Balasubramanian Moovarkumudalvan (18300811) Dindial Ramotar (208416) |
| dc.date.none.fl_str_mv | 2022-06-15T06:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1038/s41598-022-14053-9 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/The_histone_H2B_Arg95_residue_links_the_pheromone_response_pathway_to_rapamycin-induced_G1_arrest_in_yeast/25609854 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biological sciences Biochemistry and cell biology Cell cycle arrest Pheromone pathway Immunosuppressant Gene expression Yeast |
| dc.title.none.fl_str_mv | The histone H2B Arg95 residue links the pheromone response pathway to rapamycin-induced G1 arrest in yeast |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <div><p>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.</p><p> </p></div><h2>Other Information</h2> <p> Published in: Scientific Reports<br> License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1038/s41598-022-14053-9" target="_blank">https://dx.doi.org/10.1038/s41598-022-14053-9</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_45088cdbf713bcb0195c4b76f694caa8 |
| identifier_str_mv | 10.1038/s41598-022-14053-9 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/25609854 |
| publishDate | 2022 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | The histone H2B Arg95 residue links the pheromone response pathway to rapamycin-induced G1 arrest in yeastAbdallah Alhaj Sulaiman (18372912)Reem Ali (9913494)Mustapha Aouida (417652)Balasubramanian Moovarkumudalvan (18300811)Dindial Ramotar (208416)Biological sciencesBiochemistry and cell biologyCell cycle arrestPheromone pathwayImmunosuppressantGene expressionYeast<div><p>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.</p><p> </p></div><h2>Other Information</h2> <p> Published in: Scientific Reports<br> License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1038/s41598-022-14053-9" target="_blank">https://dx.doi.org/10.1038/s41598-022-14053-9</a></p>2022-06-15T06:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1038/s41598-022-14053-9https://figshare.com/articles/journal_contribution/The_histone_H2B_Arg95_residue_links_the_pheromone_response_pathway_to_rapamycin-induced_G1_arrest_in_yeast/25609854CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/256098542022-06-15T06:00:00Z |
| spellingShingle | The histone H2B Arg95 residue links the pheromone response pathway to rapamycin-induced G1 arrest in yeast Abdallah Alhaj Sulaiman (18372912) Biological sciences Biochemistry and cell biology Cell cycle arrest Pheromone pathway Immunosuppressant Gene expression Yeast |
| status_str | publishedVersion |
| title | The histone H2B Arg95 residue links the pheromone response pathway to rapamycin-induced G1 arrest in yeast |
| title_full | The histone H2B Arg95 residue links the pheromone response pathway to rapamycin-induced G1 arrest in yeast |
| title_fullStr | The histone H2B Arg95 residue links the pheromone response pathway to rapamycin-induced G1 arrest in yeast |
| title_full_unstemmed | The histone H2B Arg95 residue links the pheromone response pathway to rapamycin-induced G1 arrest in yeast |
| title_short | The histone H2B Arg95 residue links the pheromone response pathway to rapamycin-induced G1 arrest in yeast |
| title_sort | The histone H2B Arg95 residue links the pheromone response pathway to rapamycin-induced G1 arrest in yeast |
| topic | Biological sciences Biochemistry and cell biology Cell cycle arrest Pheromone pathway Immunosuppressant Gene expression Yeast |