δEF1 upregulates CDK4 transcription via the E2‑box element on the CDK4 promoter

Hu,Fen; Wang,Kai; Zhang,Yunfeng; Gou,Lixia; Luo,Mengmeng; Zhang,Xiujun; Yang,Shuang

doi:10.3892/etm.2013.1376

δEF1 upregulates CDK4 transcription via the E2‑box element on the CDK4 promoter

Authors:
- Fen Hu
- Kai Wang
- Yunfeng Zhang
- Lixia Gou
- Mengmeng Luo
- Xiujun Zhang
- Shuang Yang
View Affiliations

Affiliations: College of Life Sciences, Hebei United University, Tangshan, Hebei 063000, P.R. China, Department of Life Sciences, Tangshan Normal University, Tangshan, Hebei 063000, P.R. China, Medical College of Nankai University, Tianjin 300071, P.R. China
Published online on: October 31, 2013 https://doi.org/10.3892/etm.2013.1376
Pages: 161-164

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The zinc finger‑homeodomain transcription factor, δ‑crystallin enhancer factor 1 (δEF1) has been identified as a regulatory factor involved in the promotion of breast cancer cell proliferation via the downregulation of p21 and the upregulation of cyclin‑dependent kinase‑2 (CDK2) and CDK4 expression. However, the molecular mechanisms underlying the regulation of CDK4 expression by δEF1 have not yet been elucidated. The present study demonstrated that the ectopic expression of δEF1 in MDA‑MB‑231 breast cancer cells significantly increased the activity of the CDK4 promoter. Deletion of the E2‑box (CACGTG), which is located at position ‑197/‑191 on the human CDK4 promoter, significantly attenuated the activation of CDK4 transcription by δEF1. In addition, a CDK4 promoter‑M construct was generated via site‑directed mutagenesis of the E2‑box on the human CDK4 promoter. Luciferase assay showed that the activation of CDK4 promoter‑M activity by δEF1 was markedly decreased compared with the CDK4‑promoter‑0.4k promoter. Knockdown of δEF1 using RNA interference resulted in the inhibition of CDK4 promoter activity. These observations suggest that δEF1 upregulates CDK4 transcription via the E2‑box element on the CDK4 promoter.

View Figures

View References

1	Parkin DM, Bray F, Ferlay J and Pisani P: Global cancer statistics, 2002. CA Cancer J Clin. 55:74–108. 2005. View Article : Google Scholar
2	Draetta G: Cell cycle control in eukaryotes: molecular mechanisms of cdc2 activation. Trends Biochem Sci. 15:378–383. 1990. View Article : Google Scholar : PubMed/NCBI
3	Sherr CJ: G1 phase progression: cycling on cue. Cell. 79:551–555. 1994. View Article : Google Scholar : PubMed/NCBI
4	Caldon CE, Daly RJ, Sutherland RL and Musgrove EA: Cell cycle control in breast cancer cells. J Cell Biochem. 97:261–274. 2006. View Article : Google Scholar : PubMed/NCBI
5	Funahashi J, Kamachi Y, Goto K and Kondoh H: Identification of nuclear factor delta EF1 and its binding site essential for lens-specific activity of the delta 1-crystallin enhancer. Nucleic Acids Res. 19:3543–3547. 1991. View Article : Google Scholar : PubMed/NCBI
6	Yang S, Zhao L, Yang J, Chai D, Zhang M, Zhang J, Ji X and Zhu T: deltaEF1 represses BMP-2-induced differentiation of C2C12 myoblasts into the osteoblast lineage. J Biomed Sci. 14:663–679. 2007. View Article : Google Scholar : PubMed/NCBI
7	Hu F, Wang C, Guo S, Sun W, Mi D, Gao Y, Zhang J, Zhu T and Yang S: δEF1 promotes osteolytic metastasis of MDA-MB-231 breast cancer cells by regulating MMP-1 expression. Biochim Biophys Acta. 1809:200–210. 2011.
8	Hu F, Wang C, Du J, Sun W, Yan J, Mi D, Zhang J, Qiao Y, Zhu T and Yang S: DeltaEF1 promotes breast cancer cell proliferation through down-regulating p21 expression. Biochim Biophys Acta. 1802:301–312. 2010. View Article : Google Scholar : PubMed/NCBI
9	Sekido R, Murai K, Kamachi Y and Kondoh H: Two mechanisms in the action of repressor deltaEF1: binding site competition with an activator and active repression. Genes Cells. 2:771–783. 1997. View Article : Google Scholar : PubMed/NCBI
10	Sekido R, Murai K, Funahashi J, Kamachi Y, Fujisawa-Sehara A, Nabeshima Y and Kondoh H: The delta-crystallin enhancer-binding protein delta EF1 is a repressor of E2-box-mediated gene activation. Mol Cell Biol. 14:5692–5700. 1994. View Article : Google Scholar : PubMed/NCBI
11	Hu F, Wang C, Du J, Sun W, Yan J, Mi D, Zhang J, Qiao Y, Zhu T and Yang S: DeltaEF1 promotes breast cancer cell proliferation through down-regulating p21 expression. Biochim Biophys Acta. 1802:301–312. 2010. View Article : Google Scholar : PubMed/NCBI
12	Yang S, Du J, Wang Z, Yuan W, Qiao Y, Zhang M, Zhang J, Gao S, Yin J, Sun B and Zhu T: BMP-6 promotes E-cadherin expression through repressing deltaEF1 in breast cancer cells. BMC Cancer. 7:2112007. View Article : Google Scholar : PubMed/NCBI
13	Murray D, Precht P, Balakir R and Horton WE Jr: The transcription factor deltaEF1 is inversely expressed with type II collagen mRNA and can repress Col2a1 promoter activity in transfected chondrocytes. J Biol Chem. 275:3610–3618. 2000. View Article : Google Scholar : PubMed/NCBI
14	Dillner NB and Sanders MM: Transcriptional activation by the zinc-finger homeodomain protein delta EF1 in estrogen signaling cascades. DNA Cell Biol. 23:25–34. 2004. View Article : Google Scholar : PubMed/NCBI
15	Du J, Yang S, An D, Hu F, Yuan W, Zhai C and Zhu T: BMP-6 inhibits microRNA-21 expression in breast cancer through repressing deltaEF1 and AP-1. Cell Res. 19:487–496. 2009. View Article : Google Scholar : PubMed/NCBI