Periodic expression of Kv10.1 driven by pRb/E2F1 contributes to G2/M progression of cancer and non-transformed cells.
Cell Cycle
; 15(6): 799-811, 2016.
Article
em En
| MEDLINE
| ID: mdl-27029528
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.
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01-internacional
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MEDLINE
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Animals
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Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article