Transduced p16(INK4a) peptides inhibit hypophosphorylation of the retinoblastoma protein and cell cycle progression prior to activation of Cdk2 complexes in late G1

David R. Gius, Sergei A. Ezhevsky, Michelle Becker-Hapak, Hikaru Nagahara, Michael C. Wei, Steven F. Dowdy*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

115 Scopus citations

Abstract

Progression of cells through the G1 phase of the cell cycle requires cyclin D:Cdk4/6 and cyclin E:Cdk2 complexes; however, the duration and ordering of these complexes remain unclear. To address this, we synthesized a peptidyl mimetic of the Cdk4/6 inhibitor, p16(INK4a) that contained an NH2- terminal TAT protein transduction domain. Transduction of TAT-p16 wild-type peptides into cells resulted in the loss of active, hypophosphorylated pRb and elicited an early G1 cell cycle arrest, provided cyclin E:Cdk2 complexes were inactive. We conclude that cyclin D:Cdk4/6 activity is required for early G1 phase cell cycle progression up to, but not beyond, activation of cyclin E:Cdk2 complexes at the restriction point and is thus nonredundant with cyclin E:Cdk2 in late G1.

Original languageEnglish (US)
Pages (from-to)2577-2580
Number of pages4
JournalCancer Research
Volume59
Issue number11
StatePublished - Jun 1 1999

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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