title: Largen: a molecular regulator of mammalian cell size control.
abstract: Little is known about how mammalian cells maintain cell size homeostasis. We conducted a novel genetic screen to identify cell-size-controlling genes and isolated Largen, the product of a gene (PRR16) that increased cell size upon overexpression in human cells. In vitro evidence indicated that Largen preferentially stimulates the translation of specific subsets of mRNAs, including those encoding proteins affecting mitochondrial functions. The involvement of Largen in mitochondrial respiration was consistent with the increased mitochondrial mass and greater ATP production in Largen-overexpressing cells. Furthermore, Largen overexpression led to increased cell size in vivo, as revealed by analyses of conditional Largen transgenic mice. Our results establish Largen as an important link between mRNA translation, mitochondrial functions, and the control of mammalian cell size.
authors.affiliation: The Campbell Family Cancer Research Institute, Ontario Cancer Institute, University Health Network, Toronto, ON M5G 2C1, Canada; Departments of Medical Biophysics and Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, and Department of Oncology, McGill University, Montreal, QC H3T 1E2, Canada.
authors.forename: Valentina
authors.initials: V
authors.lastname: Gandin
authors.affiliation: The Campbell Family Cancer Research Institute, Ontario Cancer Institute, University Health Network, Toronto, ON M5G 2C1, Canada; Departments of Medical Biophysics and Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada.
authors.forename: Masato
authors.initials: M
authors.lastname: Sasaki
authors.affiliation: The Campbell Family Cancer Research Institute, Ontario Cancer Institute, University Health Network, Toronto, ON M5G 2C1, Canada; Departments of Medical Biophysics and Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada.
authors.forename: Susan
authors.initials: S
authors.lastname: McCracken
authors.affiliation: The Campbell Family Cancer Research Institute, Ontario Cancer Institute, University Health Network, Toronto, ON M5G 2C1, Canada; Departments of Medical Biophysics and Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada.
authors.forename: Wanda
authors.initials: W
authors.lastname: Li
authors.affiliation: The Campbell Family Cancer Research Institute, Ontario Cancer Institute, University Health Network, Toronto, ON M5G 2C1, Canada; Departments of Medical Biophysics and Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada.
authors.forename: Jennifer Liepa
authors.initials: JL
authors.lastname: Silvester
authors.affiliation: The Campbell Family Cancer Research Institute, Ontario Cancer Institute, University Health Network, Toronto, ON M5G 2C1, Canada; Departments of Medical Biophysics and Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Elia
authors.affiliation: Departments of Medical Biophysics and Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada; Division of Signaling Biology, Ontario Cancer Institute, Toronto, ON M5G 1L7, Canada.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Neurology, Kurashiki Heisei Hospital, Kurashiki, Okayama 710-0826, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Wakutani
authors.affiliation: The Campbell Family Cancer Research Institute, Ontario Cancer Institute, University Health Network, Toronto, ON M5G 2C1, Canada.
authors.forename: Roumiana
authors.initials: R
authors.lastname: Alexandrova
authors.affiliation: Departments of Medical Biophysics and Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada.
authors.forename: Yathor D
authors.initials: YD
authors.lastname: Oo
authors.affiliation: Division of Cancer Genomics and Proteomics, Ontario Cancer Institute, Toronto, ON M5G 2M9, Canada.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Mullen
authors.affiliation: The Campbell Family Cancer Research Institute, Ontario Cancer Institute, University Health Network, Toronto, ON M5G 2C1, Canada; Departments of Medical Biophysics and Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Inoue
authors.affiliation: The Campbell Family Cancer Research Institute, Ontario Cancer Institute, University Health Network, Toronto, ON M5G 2C1, Canada; Departments of Medical Biophysics and Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada.
authors.forename: Momoe
authors.initials: M
authors.lastname: Itsumi
authors.affiliation: The Campbell Family Cancer Research Institute, Ontario Cancer Institute, University Health Network, Toronto, ON M5G 2C1, Canada; Departments of Medical Biophysics and Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada.
authors.forename: Valentina
authors.initials: V
authors.lastname: Lapin
authors.affiliation: The Campbell Family Cancer Research Institute, Ontario Cancer Institute, University Health Network, Toronto, ON M5G 2C1, Canada; Departments of Medical Biophysics and Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada.
authors.forename: Jillian
authors.initials: J
authors.lastname: Haight
authors.affiliation: The Campbell Family Cancer Research Institute, Ontario Cancer Institute, University Health Network, Toronto, ON M5G 2C1, Canada; Departments of Medical Biophysics and Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada.
authors.forename: Andrew
authors.initials: A
authors.lastname: Wakeham
authors.affiliation: The Campbell Family Cancer Research Institute, Ontario Cancer Institute, University Health Network, Toronto, ON M5G 2C1, Canada; Departments of Medical Biophysics and Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada.
authors.forename: Arda
authors.initials: A
authors.lastname: Shahinian
authors.affiliation: Departments of Medical Biophysics and Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada; Division of Signaling Biology, Ontario Cancer Institute, Toronto, ON M5G 1L7, Canada.
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Ikura
authors.affiliation: Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, and Department of Oncology, McGill University, Montreal, QC H3T 1E2, Canada.
authors.forename: Ivan
authors.initials: I
authors.lastname: Topisirovic
authors.affiliation: Department of Biochemistry, McGill University, Montreal, QC H3A 1A3, Canada.
authors.forename: Nahum
authors.initials: N
authors.lastname: Sonenberg
authors.affiliation: The Campbell Family Cancer Research Institute, Ontario Cancer Institute, University Health Network, Toronto, ON M5G 2C1, Canada; Departments of Medical Biophysics and Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada. Electronic address: tmak@uhnresearch.ca.
authors.forename: Tak W
authors.initials: TW
authors.lastname: Mak
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D048429:Cell Size / Q000187:drug effects*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D005822:Genetic Vectors; D057166:High-Throughput Screening Assays; D006801:Humans; D019169:Jurkat Cells; D051379:Mice; D008822:Mice, Transgenic; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000494:pharmacology
chemical_list: C588258:PRR16 protein, human; D011506:Proteins; D012333:RNA, Messenger; D020123:Sirolimus