ArticleThe Journal of biological chemistry2011
The ETS family transcription factor ELK-1 regulates induction of the cell cycle-regulatory gene p21(Waf1/Cip1) and the BAX gene in sodium arsenite-exposed human keratinocyte HaCaT cells.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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24 citing papers in PubMed, 39 citations in OpenAlex.
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- C4orf19 inhibits colorectal cancer cell proliferation by competitively binding to Keap1 with TRIM25 via the USP17/Elk-1/CDK6 axis.Oncogene · 2023Article
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- Extracellular Signal-Regulated Kinase: A Regulator of Cell Growth, Inflammation, Chondrocyte and Bone Cell Receptor-Mediated Gene Expression.International journal of molecular sciences · 2019Review
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- EGR-1/Bax pathway plays a role in vitamin E δ-tocotrienol-induced apoptosis in pancreatic cancer cells.The Journal of nutritional biochemistry · 2015Article
- Id3 induces an Elk-1-caspase-8-dependent apoptotic pathway in squamous carcinoma cells.Cancer medicine · 2015Article
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4 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cyclin-dependent kinase inhibitor (CDKN1A), often referred to as p21(Waf1/Cip1) (p21), is induced by a variety of environmental stresses. Transcription factor ELK-1 is a member of the ETS oncogene superfamily. Here, we show that ELK-1 directly trans-activates the p21 gene, independently of p53 and EGR-1, in sodium arsenite (NaASO(2))-exposed HaCaT cells. Promoter deletion analysis and site-directed mutagenesis identified the presence of an ELK-1-binding core motif between -190 and -170 bp of the p21 promoter that confers inducibility by NaASO(2). Chromatin immunoprecipitation and electrophoretic mobility shift analyses confirmed the specific binding of ELK-1 to its putative binding sequence within the p21 promoter. In addition, NaASO(2)-induced p21 promoter activity was enhanced by exogenous expression of ELK-1 and reduced by expression of siRNA targeted to ELK-1 mRNA. The importance of ELK-1 in response to NaASO(2) was further confirmed by the observation that stable expression of ELK-1 siRNA in HaCaT cells resulted in the attenuation of NaASO(2)-induced p21 expression. Although ELK-1 was activated by ERK, JNK, and p38 MAPK in response to NaASO(2), ELK-1-mediated activation of the p21 promoter was largely dependent on ERK. In addition, EGR-1 induced by ELK-1 seemed to be involved in NaASO(2)-induced expression of BAX. This supports the view that the ERK/ELK-1 cascade is involved in p53-independent induction of p21 and BAX gene expression.
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