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Human arrest defective 1 acetylates and activates beta-catenin, promoting lung cancer cell proliferation

Cited 111 time in Web of Science Cited 114 time in Scopus
Authors
Lim, J. H.; Park, J. W.; Chun, Y. S.
Issue Date
2006-11-17
Publisher
American Association for Cancer Research
Citation
Cancer Res. 2006 Nov 15;66(22):10677-82.
Keywords
AcetylationAcetyltransferases/genetics/*metabolismCarcinoma, Non-Small-Cell Lung/enzymology/*metabolism/pathologyCell Growth Processes/physiologyCell Line, TumorCyclin D1/genetics/metabolismG1 Phase/physiologyHumansLung Neoplasms/enzymology/*metabolism/pathologyPromoter Regions, GeneticProtein BindingRNA, Small Interfering/geneticsTCF Transcription Factors/metabolismbeta Catenin/antagonists & inhibitors/genetics/*metabolism
Abstract
Arrest defective 1 (ARD1), an acetyltransferase, is essential for the yeast life cycle. Although its human homologue (hARD1) has been identified, its biological functions in human cells remain unclear. In the present study, we examined the biological function of hARD1. In H1299 and A549 lung cancer cells, hARD1-silencing RNA inhibited cell proliferation and induced G(1) arrest. Cyclin D1 was also found to be down-regulated in these growth-arrested cells, and the ectopic expression of cyclin D1 rescued cell growth. hARD1 knockdown repressed the promoter activity of the cyclin D1 gene, which inhibited the transcription of cyclin D1. Moreover, hARD1 knockdown reduced the binding of beta-catenin/TCF4 transcription factor to cyclin D1 promoter and repressed its transcriptional activity. Inversely, hARD1 expression increased the transcriptional activity of beta-catenin. Both endogenous and ectopically expressed hARD1 was coimmunoprecipitated with beta-catenin. hARD1 knockdown did not affect beta-catenin expression or degradation but noticeably reduced acetylated beta-catenin. The beta-catenin binding and acetylation by hARD1 were observed in vitro. Therefore, it is suggested that hARD1 participates in proliferation of lung cancer cells via the activation of beta-catenin.
ISSN
0008-5472 (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17108104

https://hdl.handle.net/10371/22955
DOI
https://doi.org/10.1158/0008-5472.CAN-06-3171
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College of Medicine/School of Medicine (의과대학/대학원)Pharmacology (약리학전공)Journal Papers (저널논문_약리학전공)
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