Periodic expression of Kv10.1 driven by pRb/E2F1 contributes to G2/M progression of cancer and non-transformed cells. Issue 6 (18th March 2016)

• Record Type: Journal Article
• Authors: Urrego, Diana; Movsisyan, Naira; Ufartes, Roser; Pardo, Luis A.
• Is Part Of: Cell cycle. Volume 15:Issue 6(2016)
• Page Start: 799
• Page End: 811
• Publication Date: 2016-03-18
• Subjects: cell cycle -- potassium channel -- Kv10.1 -- E2F1 -- pRb; Cell cycle -- Periodicals; 571.84377
• DOI: 10.1080/15384101.2016.1138187
• Languages: English
• ISSNs: 1538-4101

Abstract

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.