Mitotic arrest and cell fate: why and how mitotic inhibition of transcription drives mutually exclusive events

Cell Cycle. 2007 Jan 1;6(1):70-4. doi: 10.4161/cc.6.1.3682. Epub 2007 Jan 9.

Abstract

Here I discuss how the same mechanism--namely, inhibition of transcription during mitosis--can explain (1) apoptosis during mitotic arrest, (2) mitotic slippage, (3) G1 arrest after mitotic slippage and (4) secondary apoptosis after mitotic slippage. In fact, during mitotic arrest transcription is absent, thus depleting those short-lived proteins that have short-lived RNAs. Depletion of anti-apoptotic proteins (IAP, Mcl-1) can trigger apoptosis during prolonged mitotic arrest (apoptosis I). On the other hand, simultaneous depletion of cyclin B allows a cell to exit mitosis without division (mitotic slippage), thus preventing apoptosis I. Depletion of Mdm-2 causes accumulation of p53 during mitotic arrest. If a cell exits mitosis, transcription resumes. In turn the accumulated p53 induces p21 and Bax (and other pro-apoptotic proteins). In turn p21 can cause G1 arrest, whereas Bax can cause apoptosis II. Also, I discuss that mitotic depletion of short-lived proteins collaborates with mitotic phosphorylation of p53, Bcl-2 and BclxL. Finally this article clarifies notions of apoptosis-prone and -reluctant cells and mitotic catastrophe.

Publication types

  • Review

MeSH terms

  • Animals
  • Apoptosis / genetics*
  • Apoptosis / physiology
  • Cell Differentiation / genetics*
  • Cell Differentiation / physiology
  • Growth Inhibitors / genetics*
  • Growth Inhibitors / physiology
  • Humans
  • Mitosis / genetics*
  • Mitosis / physiology
  • Transcription, Genetic / physiology*

Substances

  • Growth Inhibitors