title: Glucose restriction induces transient G2 cell cycle arrest extending cellular chronological lifespan.
abstract: While glucose is the fundamental source of energy in most eukaryotes, it is not always abundantly available in natural environments, including within the human body. Eukaryotic cells are therefore thought to possess adaptive mechanisms to survive glucose-limited conditions, which remain unclear. Here, we report a novel mechanism regulating cell cycle progression in response to abrupt changes in extracellular glucose concentration. Upon reduction of glucose in the medium, wild-type fission yeast cells undergo transient arrest specifically at G2 phase. This cell cycle arrest is dependent on the Wee1 tyrosine kinase inhibiting the key cell cycle regulator, CDK1/Cdc2. Mutant cells lacking Wee1 are not arrested at G2 upon glucose limitation and lose viability faster than the wild-type cells under glucose-depleted quiescent conditions, suggesting that this cell cycle arrest is required for extension of chronological lifespan. Our findings indicate the presence of a novel cell cycle checkpoint monitoring glucose availability, which may be a good molecular target for cancer therapy.
authors.affiliation: Institute of Life Science, Kurume University, Hyakunen-Khoen 1-1, Kurume, Fukuoka 839-0864, Japan.
authors.forename: Fumie
authors.initials: F
authors.lastname: Masuda
authors.affiliation: Department of Biology, Faculty of Science and Engineering, Konan University, 8-9-1 Okamoto, Higashinada-ku, Kobe 658-8501, Japan.
authors.forename: Mahiro
authors.initials: M
authors.lastname: Ishii
authors.affiliation: Okinawa Institute of Science and Technology Graduate School, Tancha 1919-1, Onna, Okinawa 904-0495, Japan.
authors.forename: Ayaka
authors.initials: A
authors.lastname: Mori
authors.affiliation: Okinawa Institute of Science and Technology Graduate School, Tancha 1919-1, Onna, Okinawa 904-0495, Japan.
authors.forename: Lisa
authors.initials: L
authors.lastname: Uehara
authors.affiliation: Okinawa Institute of Science and Technology Graduate School, Tancha 1919-1, Onna, Okinawa 904-0495, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Yanagida
authors.affiliation: Department of Biology, Faculty of Science and Engineering, Konan University, 8-9-1 Okamoto, Higashinada-ku, Kobe 658-8501, Japan.|Institute for Integrative Neurobiology, Konan University, 8-9-1 Okamoto, Higashinada-ku, Kobe 658-8501, Japan.
authors.forename: Kojiro
authors.initials: K
authors.lastname: Takeda
authors.affiliation: Institute of Life Science, Kurume University, Hyakunen-Khoen 1-1, Kurume, Fukuoka 839-0864, Japan.
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Saitoh
mesh_terms: D016203:CDC2 Protein Kinase / Q000235:genetics; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics*; D002455:Cell Division / Q000235:genetics*; D003470:Culture Media / Q000737:chemistry; D004249:DNA Damage / Q000235:genetics; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects* / Q000235:genetics; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics*; D012568:Schizosaccharomyces / Q000235:genetics / Q000254:growth & development; D029702:Schizosaccharomyces pombe Proteins / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; D003470:Culture Media; D009687:Nuclear Proteins; D029702:Schizosaccharomyces pombe Proteins; C068689:wee1 protein, S pombe; D011505:Protein-Tyrosine Kinases; D016203:CDC2 Protein Kinase; D005947:Glucose