title: δEF1 upregulates CDK4 transcription via the E2-box element on the CDK4 promoter.
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.
authors.affiliation: College of Life Sciences, Hebei United University, Tangshan, Hebei 063000, P.R. China.
authors.forename: Fen
authors.initials: F
authors.lastname: Hu
authors.affiliation: College of Life Sciences, Hebei United University, Tangshan, Hebei 063000, P.R. China.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Life Sciences, Tangshan Normal University, Tangshan, Hebei 063000, P.R. China.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: College of Life Sciences, Hebei United University, Tangshan, Hebei 063000, P.R. China.
authors.forename: Lixia
authors.initials: L
authors.lastname: Gou
authors.affiliation: College of Life Sciences, Hebei United University, Tangshan, Hebei 063000, P.R. China.
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Luo
authors.affiliation: College of Life Sciences, Hebei United University, Tangshan, Hebei 063000, P.R. China.
authors.forename: Xiujun
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Medical College of Nankai University, Tianjin 300071, P.R. China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Yang
keywords: E2-box; cyclin-dependent kinase 4; promoter; δ-crystallin enhancer factor 1