Cdc6 requires anchorage for its expression

Shigeki Jinno, Mika Yageta, Akihisa Nagata, Hiroto Okayama

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

Fibroblasts need anchorage to extracellular matrix to transit from G1 to S phase, but no longer after oncogenic transformation. Here we report that Cdc6 protein essential for the activation of replication origins requires anchorage or oncogenic stimulation for its execution. Upon anchorage loss, Cdc6 expression is shut off both transcriptionally and post-transcriptionally in a rat fibroblast despite enforced activation of E2F-dependent promoters. However, stimulation of this cell with oncogenic growth factors suppresses this shutoff and concurrently activates Cdk2 and Cdk6/4, thereby overriding the anchorage requirement for the G1-S transition and consequently enabling cells to perform anchorage-independent S phase entry. Analysis with enforced expression of Cdc6 indicates that the G1 cyclin-dependent kinases and Cdc6 constitute major cell cycle targets for the restriction of the G1-S transition by anchorage loss.

Original languageEnglish
Pages (from-to)1777-1784
Number of pages8
JournalOncogene
Volume21
Issue number11
DOIs
Publication statusPublished - 2002 Mar 7
Externally publishedYes

Keywords

  • Anchorage
  • Cdc6
  • Cdk6
  • Cyclin D3
  • NRK

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Fingerprint

Dive into the research topics of 'Cdc6 requires anchorage for its expression'. Together they form a unique fingerprint.

Cite this