Periodic expression of Kv10.1 driven by pRb/E2F1 contributes to G2/M progression of cancer and non-transformed cells

Cell Cycle. 2016;15(6):799-811. doi: 10.1080/15384101.2016.1138187.

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.

Keywords: E2F1; Kv10.1; cell cycle; pRb; potassium channel.

MeSH terms

  • Animals
  • CDC2 Protein Kinase / genetics
  • CDC2 Protein Kinase / metabolism
  • Cell Proliferation
  • E2F1 Transcription Factor / genetics*
  • E2F1 Transcription Factor / metabolism
  • Embryo, Mammalian
  • Ether-A-Go-Go Potassium Channels / genetics*
  • Ether-A-Go-Go Potassium Channels / metabolism
  • Fibroblasts / cytology
  • Fibroblasts / metabolism*
  • G2 Phase Cell Cycle Checkpoints / genetics*
  • Gene Expression Regulation
  • HeLa Cells
  • Humans
  • Ion Transport
  • Mice
  • Mice, Knockout
  • Papillomavirus E7 Proteins / genetics
  • Papillomavirus E7 Proteins / metabolism
  • Potassium / metabolism
  • Promoter Regions, Genetic
  • Protein Binding
  • Retinoblastoma Protein / genetics*
  • Retinoblastoma Protein / metabolism
  • Signal Transduction
  • Transcription, Genetic

Substances

  • E2F1 Transcription Factor
  • E2F1 protein, human
  • Ether-A-Go-Go Potassium Channels
  • KCNH1 protein, human
  • Papillomavirus E7 Proteins
  • Retinoblastoma Protein
  • CDC2 Protein Kinase
  • Potassium