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

Research output: Contribution to journalArticlepeer-review

117 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
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Transduced p16(INK4a) peptides inhibit hypophosphorylation of the retinoblastoma protein and cell cycle progression prior to activation of Cdk2 complexes in late G1'. Together they form a unique fingerprint.

Cite this