title: A global genomic view on LNX siRNA-mediated cell cycle arrest.
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.
authors.affiliation: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai, 200433, People's Republic of China.
authors.forename: Dan
authors.initials: D
authors.lastname: Zheng
authors.forename: Shaohua
authors.initials: S
authors.lastname: Gu
authors.forename: Yao
authors.initials: Y
authors.lastname: Li
authors.forename: Chaoneng
authors.initials: C
authors.lastname: Ji
authors.forename: Yi
authors.initials: Y
authors.lastname: Xie
authors.forename: Yumin
authors.initials: Y
authors.lastname: Mao
mesh_terms: D002453:Cell Cycle / Q000502:physiology*; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000235:genetics*; D055785:Gene Knockdown Techniques; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D009841:Oligonucleotides / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*; D051176:beta Catenin / Q000378:metabolism
chemical_list: D017931:DNA Primers; D016328:NF-kappa B; D009841:Oligonucleotides; D034741:RNA, Small Interfering; D016212:Transforming Growth Factor beta; D016159:Tumor Suppressor Protein p53; D051176:beta Catenin; C484733:LNX1 protein, human; D044767:Ubiquitin-Protein Ligases; D020928:Mitogen-Activated Protein Kinases