Kim Wonho, Kim Hag Dong, Jung Youjin, Kim Joon, Chung Jongkyeong
From the Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 305-701, Republic of Korea, National Creative Research Initiatives Center for Energy Homeostasis Regulation, Institute of Molecular Biology and Genetics and School of Biological Sciences, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul 151-742, Republic of Korea, and.
Laboratory of Biochemistry, Division of Life Sciences, Korea University, Seoul 136-701, Republic of Korea.
J Biol Chem. 2015 May 22;290(21):13591-604. doi: 10.1074/jbc.M114.607036. Epub 2015 Apr 9.
During animal development, various signaling pathways converge to regulate cell growth. In this study, we identified LTV1 as a novel cell growth regulator in Drosophila. LTV1 mutant larvae exhibited developmental delays and lethality at the second larval stage. Using biochemical studies, we discovered that LTV1 interacted with ribosomal protein S3 and co-purified with free 40S ribosome subunits. We further demonstrated that LTV1 is crucial for ribosome biogenesis through 40S ribosome subunit synthesis and preribosomal RNA processing, suggesting that LTV1 is required for cell growth by regulating protein synthesis. We also demonstrated that Drosophila Myc (dMyc) directly regulates LTV1 transcription and requires LTV1 to stimulate ribosome biogenesis. Importantly, the loss of LTV1 blocked the cell growth and endoreplication induced by dMyc. Combined, these results suggest that LTV1 is a key downstream factor of dMyc-induced cell growth by properly maintaining ribosome biogenesis.
在动物发育过程中，多种信号通路汇聚以调节细胞生长。在本研究中，我们鉴定出LTV1是果蝇中一种新型的细胞生长调节因子。LTV1突变体幼虫在第二幼虫阶段表现出发育延迟和致死性。通过生化研究，我们发现LTV1与核糖体蛋白S3相互作用，并与游离的40S核糖体亚基共纯化。我们进一步证明，LTV1通过40S核糖体亚基合成和前核糖体RNA加工对核糖体生物发生至关重要，这表明LTV1通过调节蛋白质合成来促进细胞生长。我们还证明，果蝇Myc（dMyc）直接调节LTV1转录，并需要LTV1来刺激核糖体生物发生。重要的是，LTV1的缺失阻断了dMyc诱导的细胞生长和核内复制。综合这些结果表明，LTV1通过适当维持核糖体生物发生，是dMyc诱导细胞生长的关键下游因子。
