Human arrest defective 1 acetylates and activates beta-catenin, promoting lung cancer cell proliferation
- PMID: 17108104
- DOI: 10.1158/0008-5472.CAN-06-3171
Human arrest defective 1 acetylates and activates beta-catenin, promoting lung cancer cell proliferation
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.
Similar articles
-
Hypoxia-inducible factor-1alpha obstructs a Wnt signaling pathway by inhibiting the hARD1-mediated activation of beta-catenin.Cancer Res. 2008 Jul 1;68(13):5177-84. doi: 10.1158/0008-5472.CAN-07-6234. Cancer Res. 2008. PMID: 18593917
-
Arrest defective 1 autoacetylation is a critical step in its ability to stimulate cancer cell proliferation.Cancer Res. 2010 Jun 1;70(11):4422-32. doi: 10.1158/0008-5472.CAN-09-3258. Epub 2010 May 25. Cancer Res. 2010. PMID: 20501853
-
The protein acetyltransferase ARD1: a novel cancer drug target?Curr Cancer Drug Targets. 2008 Nov;8(7):545-53. doi: 10.2174/156800908786241113. Curr Cancer Drug Targets. 2008. PMID: 18991565 Review.
-
Identification and characterization of the human ARD1-NATH protein acetyltransferase complex.Biochem J. 2005 Mar 15;386(Pt 3):433-43. doi: 10.1042/BJ20041071. Biochem J. 2005. PMID: 15496142 Free PMC article.
-
Diverse roles of arrest defective 1 in cancer development.Arch Pharm Res. 2019 Dec;42(12):1040-1051. doi: 10.1007/s12272-019-01195-0. Epub 2019 Dec 7. Arch Pharm Res. 2019. PMID: 31813105 Review.
Cited by
-
N-α-acetyltransferase 10 (NAA10) in development: the role of NAA10.Exp Mol Med. 2018 Jul 27;50(7):1-11. doi: 10.1038/s12276-018-0105-2. Exp Mol Med. 2018. PMID: 30054454 Free PMC article. Review.
-
ARD1 contributes to IKKβ-mediated breast cancer tumorigenesis.Cell Death Dis. 2018 Aug 28;9(9):860. doi: 10.1038/s41419-018-0921-2. Cell Death Dis. 2018. PMID: 30154412 Free PMC article.
-
Wnt-β-catenin signaling protects against hepatic ischemia and reperfusion injury in mice.Gastroenterology. 2011 Aug;141(2):707-18, 718.e1-5. doi: 10.1053/j.gastro.2011.04.051. Epub 2011 May 4. Gastroenterology. 2011. PMID: 21679710 Free PMC article.
-
daf-31 encodes the catalytic subunit of N alpha-acetyltransferase that regulates Caenorhabditis elegans development, metabolism and adult lifespan.PLoS Genet. 2014 Oct 16;10(10):e1004699. doi: 10.1371/journal.pgen.1004699. eCollection 2014 Oct. PLoS Genet. 2014. PMID: 25330189 Free PMC article.
-
Severe syndromic ID and skewed X-inactivation in a girl with NAA10 dysfunction and a novel heterozygous de novo NAA10 p.(His16Pro) variant - a case report.BMC Med Genet. 2020 Jul 22;21(1):153. doi: 10.1186/s12881-020-01091-1. BMC Med Genet. 2020. PMID: 32698785 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Molecular Biology Databases
Research Materials
