title: Periodic expression of Kv10.1 driven by pRb/E2F1 contributes to G2/M progression of cancer and non-transformed cells.
abstract: Progression of cell cycle is associated with changes in K(+) channel expression and activity. In this study, we report that Kv10.1, a K(+) channel that increases cell proliferation and tumor growth, is regulated at the transcriptional level by the pRb/E2F1 pathway. De-repression of E2F1 by HPV-E7 oncoprotein leads to increased expression of Kv10.1. In proliferating cells, E2F1 transcription factor binds directly to the Kv10.1 promoter during (or close to) G2/M, resulting in transient expression of the channel. Importantly, this happens not only in cancer cells but also in non-transformed cells. Lack of Kv10.1 in both cancer and non-transformed cells resulted in prolonged G2/M phase, as indicated by phosphorylation of Cdk1 (Y15) and sustained pRb hyperphosphorylation. Our results strongly suggest that Kv10.1 expression is coupled to cell cycle progression and facilitates G2/M progression in both healthy and tumor cells.
authors.affiliation: a Oncophysiology Group, Max-Planck-Institute of Experimental Medicine , Göttingen , Germany.
authors.forename: Diana
authors.initials: D
authors.lastname: Urrego
authors.affiliation: a Oncophysiology Group, Max-Planck-Institute of Experimental Medicine , Göttingen , Germany.
authors.forename: Naira
authors.initials: N
authors.lastname: Movsisyan
authors.affiliation: b Department of Molecular Biology of Neuronal Signals , Max-Planck-Institute of Experimental Medicine , Göttingen , Germany.
authors.forename: Roser
authors.initials: R
authors.lastname: Ufartes
authors.affiliation: a Oncophysiology Group, Max-Planck-Institute of Experimental Medicine , Göttingen , Germany.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Pardo
mesh_terms: D000818:Animals; D016203:CDC2 Protein Kinase / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D050687:E2F1 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D004622:Embryo, Mammalian; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics* / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D059565:G2 Phase Cell Cycle Checkpoints / Q000235:genetics*; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D017136:Ion Transport; D051379:Mice; D018345:Mice, Knockout; D050725:Papillomavirus E7 Proteins / Q000235:genetics / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D016160:Retinoblastoma Protein / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D051638:Ether-A-Go-Go Potassium Channels; C496884:KCNH1 protein, human; D050725:Papillomavirus E7 Proteins; D016160:Retinoblastoma Protein; D016203:CDC2 Protein Kinase; D011188:Potassium
keywords: E2F1; Kv10.1; cell cycle; pRb; potassium channel