P21waf-1-Chk1 pathway monitors G1 phase microtubule integrity and is crucial for restriction point transition.

Charlie R. Mantel, Vasily M. Gelfano, Young June Kim, Andrew McDaniel, Younghee Lee, H. Scott Boswell, Hal E. Broxmeyer

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Microtubule-disruption (MTD) is often thought to arrest the mammalian cell cycle only during mitosis. However, MTD has also been demonstrated to arrest cells during interphase at a G(1)-phase point we call G(1)MTA. Microtubule integrity is now shown to be required for progression past G(1)MTA and the mammalian restriction-point. Neither p21(waf1) nor p27(kip1) are required for MTD-induced G(1)-arrest. Only p21(waf1) is crucial for normal G(1)MTA passage. The p21(waf1)-Chk1-cdc25C-cdc2-checkpoint-pathway is implicated in monitoring this passage. P21(waf1) deletion deregulates G(1)MTA transition and decreases MTD-G(1) arrest, possibly via Chk1 disregulation. Oncogene-induced overexpression of p21(waf1) produced opposite effects on the Chk1-cdc25C-cdc2 pathway and enhanced MTD-G(1) arrest. G(1)MTA thus represents a novel facet of mammalian G(1)/S checkpoint.

Original languageEnglish (US)
Pages (from-to)327-336
Number of pages10
JournalCell cycle (Georgetown, Tex.)
Volume1
Issue number5
StatePublished - 2002

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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