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A global genomic view on LNX siRNA-mediated cell cycle arrest

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Abstract

LNX protein is the first described PDZ domain-containing member of the RING finger-type E3 ubiquitin ligase family. Studies have approved that LNX could participate in signal transduction, such as Notch pathway, and play an important role in tumorigenesis. In this study, we found that down-regulation of LNX resulted in G0/G1 cell cycle arrest in G0/G1 phase in HEK293 cells. To explore the molecular mechanism of this phenomenon, we employed expression microarray to comparatively analyze the genome-wide expression between the LNX-knockdown cells and the normal cells. We also used quantitative real-time PCR to further confirm the differential expression patterns of 25 transcripts involved in cell cycle. Combined with known information about genic functions, signal pathways and cell cycle machinery, we analyzed the role of endogenous LNX in cell cycle. The results suggest that down-regulation of LNX could result in cell cycle arrest in G0/G1 phase through inhibition of β-catenin, MAPK, NFκB, c-Myc-dependent pathway and activation of p53, TGF-β-dependent pathway. This study provides new perspectives on LNX’s pleiotropic activities, especially its essential role in cell proliferation and cell cycle.

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Acknowledgments

This work was supported by National Basic Research Program of China (973 Program, 2007CB914304 and 2009CB825505), National Natural Science Foundation of China (No.: 30770427), Program for New Century Excellent Talents in University (NCET-06-0356) and Shanghai Leading Academic Discipline Project (B111).

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  1. State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai, 200433, People’s Republic of China

    Dan Zheng, Shaohua Gu, Yao Li, Chaoneng Ji, Yi Xie & Yumin Mao

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  1. Dan Zheng
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Correspondence to Yumin Mao.

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Zheng, D., Gu, S., Li, Y. et al. A global genomic view on LNX siRNA-mediated cell cycle arrest. Mol Biol Rep 38, 2771–2783 (2011). https://doi.org/10.1007/s11033-010-0422-6

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