» Articles » PMID: 21104141

A Global Genomic View on LNX SiRNA-mediated Cell Cycle Arrest

Overview
Journal Mol Biol Rep
Specialty Molecular Biology
Date 2010 Nov 25
PMID 21104141
Citations 4
Authors
Affiliations
Soon will be listed here.
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.

Citing Articles

Contributes to Cell Cycle Progression and Cisplatin Resistance.

Jang M, Park R, Park Y, Park Y, Lee J, Namkoong S Cancers (Basel). 2021; 13(16).

PMID: 34439220 PMC: 8394373. DOI: 10.3390/cancers13164066.


LNX1/LNX2 proteins: functions in neuronal signalling and beyond.

Young P Neuronal Signal. 2020; 2(2):NS20170191.

PMID: 32714586 PMC: 7373230. DOI: 10.1042/NS20170191.


The Roles of RNase-L in Antimicrobial Immunity and the Cytoskeleton-Associated Innate Response.

Ezelle H, Malathi K, Hassel B Int J Mol Sci. 2016; 17(1).

PMID: 26760998 PMC: 4730318. DOI: 10.3390/ijms17010074.


Survivin small interfering RNA suppresses glioblastoma growth by inducing cellular apoptosis.

Liu Y, Miao C, Wang Z, He X, Shen W Neural Regen Res. 2015; 7(12):924-31.

PMID: 25722677 PMC: 4341288. DOI: 10.3969/j.issn.1673-5374.2012.12.008.

References
1.
Kaltschmidt B, Kaltschmidt C, Hehner S, Droge W, Schmitz M . Repression of NF-kappaB impairs HeLa cell proliferation by functional interference with cell cycle checkpoint regulators. Oncogene. 1999; 18(21):3213-25. DOI: 10.1038/sj.onc.1202657. View

2.
Pray T, Parlati F, Huang J, Wong B, Payan D, Bennett M . Cell cycle regulatory E3 ubiquitin ligases as anticancer targets. Drug Resist Updat. 2003; 5(6):249-58. DOI: 10.1016/s1368-7646(02)00121-8. View

3.
Falck J, Coates J, Jackson S . Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of DNA damage. Nature. 2005; 434(7033):605-11. DOI: 10.1038/nature03442. View

4.
Yamamura Y, Hua X, Bergelson S, Lodish H . Critical role of Smads and AP-1 complex in transforming growth factor-beta -dependent apoptosis. J Biol Chem. 2000; 275(46):36295-302. DOI: 10.1074/jbc.M006023200. View

5.
Chen J, Xu J, Zhao W, Hu G, Cheng H, Kang Y . Characterization of human LNX, a novel ligand of Numb protein X that is downregulated in human gliomas. Int J Biochem Cell Biol. 2005; 37(11):2273-83. DOI: 10.1016/j.biocel.2005.02.028. View