A role of P301L tau mutant in anti-apoptotic gene expression, cell cycle and apoptosis

Mol Cell Neurosci. 2003 Oct;24(2):367-79. doi: 10.1016/s1044-7431(03)00175-1.


In exploring the causative role of the most common Pro(301)-to-Leu (TauP301L) tau missense mutation associated with neurodegenerative tauopathies, we examined TauP301L-mediated apoptotic cell death and the expression of a cluster of genes involved in the inhibition of apoptosis (IAPs) in human neuroblastoma SH-SY5Y cells. Our research found that the expression of TauP301L, but not wild-type tau, down regulated the expression of IAPs, including survivin, which plays a role in the mitotic spindle checkpoint. The inhibition of IAPs coincided with the activation of the pro-apoptotic caspase 3, but preceded apoptotic cell death by TUNEL. Furthermore, TauP301L altered the expression of the cell cycle regulatory proteins and induced the cell cycle arrest at G(2)/M phase. Our studies demonstrate that TauP301L downregulates the expression of genes that protect against apoptosis and regulate cell cycle progression. These results suggest a novel mechanism of apoptotic cell death in TauP301L-expressing cells that involves survivin-mediated activation of cell cycle checkpoint.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics*
  • Apoptosis / physiology
  • Cell Cycle / genetics*
  • Cell Cycle / physiology
  • Cell Line
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / physiology*
  • Humans
  • Leucine / genetics
  • Mutation, Missense*
  • Proline / genetics
  • tau Proteins / genetics*
  • tau Proteins / physiology*


  • tau Proteins
  • Proline
  • Leucine