Proteasomal degradation of tau protein

J Neurochem. 2002 Oct;83(1):176-85. doi: 10.1046/j.1471-4159.2002.01137.x.


Filamentous inclusions composed of the microtubule-associated protein tau are a defining characteristic of a large number of neurodegenerative diseases. Here we show that tau degradation in stably transfected and non-transfected SH-SY5Y cells is blocked by the irreversible proteasome inhibitor lactacystin. Further, we find that in vitro, natively unfolded tau can be directly processed by the 20S proteasome without a requirement for ubiquitylation, and that a highly reproducible pattern of degradation intermediates is readily detectable during this process. Analysis of these intermediates shows that 20S proteasomal processing of tau is bi-directional, proceeding from both N- and C-termini, and that populations of relatively stable intermediates arise probably because of less efficient digestion of the C-terminal repeat region. Our results are consistent with an in vivo role for the proteasome in tau degradation and support the existence of ubiquitin-independent pathways for the proteasomal degradation of unfolded proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / analogs & derivatives*
  • Acetylcysteine / pharmacology
  • Blotting, Western
  • Cysteine Endopeptidases / chemistry
  • Cysteine Endopeptidases / metabolism*
  • Cysteine Proteinase Inhibitors / pharmacology
  • Humans
  • Multienzyme Complexes / antagonists & inhibitors
  • Multienzyme Complexes / chemistry
  • Multienzyme Complexes / metabolism*
  • Neuroblastoma / metabolism
  • Proteasome Endopeptidase Complex
  • Protein Folding
  • Protein Isoforms / chemistry
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Transfection
  • Tumor Cells, Cultured
  • Ubiquitin / metabolism
  • tau Proteins / chemistry
  • tau Proteins / genetics
  • tau Proteins / metabolism*


  • Cysteine Proteinase Inhibitors
  • Multienzyme Complexes
  • Protein Isoforms
  • Ubiquitin
  • tau Proteins
  • lactacystin
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex
  • Acetylcysteine