TY - JOUR
T1 - Largen
T2 - A molecular regulator of mammalian cell size control
AU - Yamamoto, Kazuo
AU - Gandin, Valentina
AU - Sasaki, Masato
AU - McCracken, Susan
AU - Li, Wanda
AU - Silvester, Jennifer Liepa
AU - Elia, Andrew J.
AU - Wang, Feng
AU - Wakutani, Yosuke
AU - Alexandrova, Roumiana
AU - Oo, Yathor D.
AU - Mullen, Peter J.
AU - Inoue, Satoshi
AU - Itsumi, Momoe
AU - Lapin, Valentina
AU - Haight, Jillian
AU - Wakeham, Andrew
AU - Shahinian, Arda
AU - Ikura, Mitsuhiko
AU - Topisirovic, Ivan
AU - Sonenberg, Nahum
AU - Mak, Tak W.
N1 - Funding Information:
This report is dedicated to the memory of Dr. Susan McCracken, who passed away during the preparation of this manuscript. We thank Drs. Rikiro Fukunaga and Andras Nagy for plasmids; Dr. Tomoo Ogi and Mayuko Shimada for assistance with plasmid construction; Dr. David M. Sabatini and colleagues for experimental materials and fruitful discussions; and Drs. Masami Horikoshi, Akatsuki Kimura, Gerry Melino, Vuk Stambolic, and Bradly Wouters for helpful input and encouragement. Finally, we are grateful to Dr. Mary Saunders for scientific editing and Denis Bouchard for cell sorting. This work was supported by a grant to T.W.M. from the Canadian Institutes of Health Research (#178866). This research was also funded in part by the Ontario Ministry of Health and Long Term Care. The views expressed do not necessarily reflect those of the OMOHLTC.
PY - 2014/3/20
Y1 - 2014/3/20
N2 - 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. Invitro evidence indicated that Largen preferentially stimulates the translation of specific subsetsof mRNAs, including those encoding proteins affecting mitochondrial functions. The involvement of Largen in mitochondrial respiration was consistentwith the increased mitochondrial mass and greater ATP production in Largen-overexpressing cells. Furthermore, Largen overexpression led to increased cell size invivo, 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.
AB - 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. Invitro evidence indicated that Largen preferentially stimulates the translation of specific subsetsof mRNAs, including those encoding proteins affecting mitochondrial functions. The involvement of Largen in mitochondrial respiration was consistentwith the increased mitochondrial mass and greater ATP production in Largen-overexpressing cells. Furthermore, Largen overexpression led to increased cell size invivo, 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.
UR - https://www.scopus.com/pages/publications/84896358878
UR - https://www.scopus.com/pages/publications/84896358878#tab=citedBy
U2 - 10.1016/j.molcel.2014.02.028
DO - 10.1016/j.molcel.2014.02.028
M3 - Article
C2 - 24656129
AN - SCOPUS:84896358878
SN - 1097-2765
VL - 53
SP - 904
EP - 915
JO - Molecular Cell
JF - Molecular Cell
IS - 6
ER -