Document Detail

A role of P301L tau mutant in anti-apoptotic gene expression, cell cycle and apoptosis.
MedLine Citation:
PMID:  14572459     Owner:  NLM     Status:  MEDLINE    
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.
Z Zhao; L Ho; J Suh; W Qin; H Pyo; P Pompl; H Ksiezak-Reding; G M Pasinetti
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecular and cellular neurosciences     Volume:  24     ISSN:  1044-7431     ISO Abbreviation:  Mol. Cell. Neurosci.     Publication Date:  2003 Oct 
Date Detail:
Created Date:  2003-10-23     Completed Date:  2004-01-23     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9100095     Medline TA:  Mol Cell Neurosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  367-79     Citation Subset:  IM    
Neuroinflammation Research Laboratories of the Department of Psychiatry, Box 1230, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA.
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MeSH Terms
Apoptosis / genetics*,  physiology
Cell Cycle / genetics*,  physiology
Cell Line
Gene Expression Regulation / genetics,  physiology*
Leucine / genetics
Mutation, Missense*
Proline / genetics
tau Proteins / genetics*,  physiology*
Reg. No./Substance:
0/tau Proteins; 147-85-3/Proline; 61-90-5/Leucine

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