Largen: A Molecular Regulator of Mammalian Cell Size Control

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• 作者：Kazuo Yamamoto¹ ; ² ; ⁸ ; Valentina Gandin³ ; Masato Sasaki¹ ; ² ; Susan McCracken¹ ; ² ; Wanda Li¹ ; ² ; Jennifer Liepa Silvester¹ ; ² ; Andrew J. Elia¹ ; ² ; Feng Wang² ; ⁴ ; Yosuke Wakutani⁵ ; Roumiana Alexandrova¹ ; Yathor D Oo² ; Peter J. Mullen⁶ ; Satoshi Inoue¹ ; ² ; Momoe Itsumi¹ ; ² ; Valentina Lapin¹ ; ² ; Jillian Haight¹ ; ² ; Andrew Wakeham¹ ; ² ; Arda Shahinian¹ ; ² ; Mitsuhiko Ikura² ; ⁴ ; Ivan Topisirovic³ ; Nahum Sonenberg⁷ ; Tak W. Mak¹ ; ² ; ^{tmak@uhnresearch.ca" class="auth_mail}
• 刊名：Molecular Cell
• 出版年：20 March, 2014
• 年：2014
• 卷：53
• 期：6
• 页码：904-915
• 全文大小：2594 K

文摘

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Summary

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聽vitro evidence indicated that Largen preferentially stimulates the translation of specific subsets聽of mRNAs, including those encoding proteins affecting mitochondrial functions. The involvement of Largen in mitochondrial respiration was consistent聽with the increased mitochondrial mass and greater ATP production in Largen-overexpressing cells. Furthermore, Largen overexpression led to increased cell size in聽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.