LAMMER Kinase Modulates Cell Cycle by Phosphorylating the MBF Repressor, Yox1, in Schizosaccharomyces pombe

Lkh1, a LAMMER kinase homolog in the fission yeast Schizosaccharomyces pombe, acts as a negative regulator of filamentous growth and flocculation. It is also involved in the response to oxidative stress. The lkh1-deletion mutant displays slower cell growth, shorter cell size, and abnormal DNA conten...

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Main Authors: Kibum Park, Joo-Yeon Lim, Je-Hoon Kim, Jieun Lee, Songju Shin, Hee-Moon Park
Format: Article
Language:English
Published: Taylor & Francis Group 2023-09-01
Series:Mycobiology
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Online Access:https://www.tandfonline.com/doi/10.1080/12298093.2023.2262806
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author Kibum Park
Joo-Yeon Lim
Je-Hoon Kim
Jieun Lee
Songju Shin
Hee-Moon Park
author_facet Kibum Park
Joo-Yeon Lim
Je-Hoon Kim
Jieun Lee
Songju Shin
Hee-Moon Park
author_sort Kibum Park
collection DOAJ
description Lkh1, a LAMMER kinase homolog in the fission yeast Schizosaccharomyces pombe, acts as a negative regulator of filamentous growth and flocculation. It is also involved in the response to oxidative stress. The lkh1-deletion mutant displays slower cell growth, shorter cell size, and abnormal DNA content compared to the wild type. These phenotypes suggest that Lkh1 controls cell size and cell cycle progression. When we performed microarray analysis using the lkh1-deletion mutant, we found that only four of the up-regulated genes in the lkh1-deletion were associated with the cell cycle. Interestingly, all of these genes are regulated by the Mlu1 cell cycle box binding factor (MBF), which is a transcription complex responsible for regulating the expression of cell cycle genes during the G1/S phase. Transcription analyses of the MBF-dependent cell-cycle genes, including negative feedback regulators, confirmed the up-regulation of these genes by the deletion of lkh1. Pull-down assay confirmed the interaction between Lkh1 and Yox1, which is a negative feedback regulator of MBF. This result supports the involvement of LAMMER kinase in cell cycle regulation by modulating MBF activity. In vitro kinase assay and NetPhosK 2.0 analysis with the Yox1T40,41A mutant allele revealed that T40 and T41 residues are the phosphorylation sites mediated by Lkh1. These sites affect the G1/S cell cycle progression of fission yeast by modulating the activity of the MBF complex.
format Article
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institution DOAJ
issn 1229-8093
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language English
publishDate 2023-09-01
publisher Taylor & Francis Group
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series Mycobiology
spelling doaj-art-3394944065d448d1b8d53cdf680909092025-08-20T02:47:33ZengTaylor & Francis GroupMycobiology1229-80932092-93232023-09-0151537237810.1080/12298093.2023.2262806LAMMER Kinase Modulates Cell Cycle by Phosphorylating the MBF Repressor, Yox1, in Schizosaccharomyces pombeKibum Park0Joo-Yeon Lim1Je-Hoon Kim2Jieun Lee3Songju Shin4Hee-Moon Park5Laboratory of Cellular Differentiation, Department of Microbiology and Molecular Biology, College of Bioscience and Biotechnology, Chungnam National University, Daejeon, Republic of KoreaDepartment of Microbiology and Immunology, Indiana University School of Medicine-Terre Haute, Terre Haute, IN, USALaboratory of Cellular Differentiation, Department of Microbiology and Molecular Biology, College of Bioscience and Biotechnology, Chungnam National University, Daejeon, Republic of KoreaLaboratory of Cellular Differentiation, Department of Microbiology and Molecular Biology, College of Bioscience and Biotechnology, Chungnam National University, Daejeon, Republic of KoreaLaboratory of Cellular Differentiation, Department of Microbiology and Molecular Biology, College of Bioscience and Biotechnology, Chungnam National University, Daejeon, Republic of KoreaLaboratory of Cellular Differentiation, Department of Microbiology and Molecular Biology, College of Bioscience and Biotechnology, Chungnam National University, Daejeon, Republic of KoreaLkh1, a LAMMER kinase homolog in the fission yeast Schizosaccharomyces pombe, acts as a negative regulator of filamentous growth and flocculation. It is also involved in the response to oxidative stress. The lkh1-deletion mutant displays slower cell growth, shorter cell size, and abnormal DNA content compared to the wild type. These phenotypes suggest that Lkh1 controls cell size and cell cycle progression. When we performed microarray analysis using the lkh1-deletion mutant, we found that only four of the up-regulated genes in the lkh1-deletion were associated with the cell cycle. Interestingly, all of these genes are regulated by the Mlu1 cell cycle box binding factor (MBF), which is a transcription complex responsible for regulating the expression of cell cycle genes during the G1/S phase. Transcription analyses of the MBF-dependent cell-cycle genes, including negative feedback regulators, confirmed the up-regulation of these genes by the deletion of lkh1. Pull-down assay confirmed the interaction between Lkh1 and Yox1, which is a negative feedback regulator of MBF. This result supports the involvement of LAMMER kinase in cell cycle regulation by modulating MBF activity. In vitro kinase assay and NetPhosK 2.0 analysis with the Yox1T40,41A mutant allele revealed that T40 and T41 residues are the phosphorylation sites mediated by Lkh1. These sites affect the G1/S cell cycle progression of fission yeast by modulating the activity of the MBF complex.https://www.tandfonline.com/doi/10.1080/12298093.2023.2262806Lkh1LAMMER kinaseYox1MBFcell cyclephosphorylation
spellingShingle Kibum Park
Joo-Yeon Lim
Je-Hoon Kim
Jieun Lee
Songju Shin
Hee-Moon Park
LAMMER Kinase Modulates Cell Cycle by Phosphorylating the MBF Repressor, Yox1, in Schizosaccharomyces pombe
Mycobiology
Lkh1
LAMMER kinase
Yox1
MBF
cell cycle
phosphorylation
title LAMMER Kinase Modulates Cell Cycle by Phosphorylating the MBF Repressor, Yox1, in Schizosaccharomyces pombe
title_full LAMMER Kinase Modulates Cell Cycle by Phosphorylating the MBF Repressor, Yox1, in Schizosaccharomyces pombe
title_fullStr LAMMER Kinase Modulates Cell Cycle by Phosphorylating the MBF Repressor, Yox1, in Schizosaccharomyces pombe
title_full_unstemmed LAMMER Kinase Modulates Cell Cycle by Phosphorylating the MBF Repressor, Yox1, in Schizosaccharomyces pombe
title_short LAMMER Kinase Modulates Cell Cycle by Phosphorylating the MBF Repressor, Yox1, in Schizosaccharomyces pombe
title_sort lammer kinase modulates cell cycle by phosphorylating the mbf repressor yox1 in schizosaccharomyces pombe
topic Lkh1
LAMMER kinase
Yox1
MBF
cell cycle
phosphorylation
url https://www.tandfonline.com/doi/10.1080/12298093.2023.2262806
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