Effects of tau phosphorylation on proteasome activity.
Dysfunction of proteasome contributes to the accumulation of the abnormally hyperphosphorylated tau in Alzheimer's disease. However, whether tau hyperphosphorylation and accumulation affect the activity of proteasome is elusive. Here we found that a moderate tau phosphorylation activated the trypsin-like activity of proteasome, whereas further phosphorylation of tau inhibited the activity of the protease in HEK293 cells stably expressing tau441. Furthermore, tau hyperphosphorylation could partially reverse lactacystin-induced inhibition of proteasome. These results suggest that phosphorylation of tau plays a dual role in modulating the activity of proteasome.
Ren
Qing-Guo
QG
Department of Pathophysiology, Hubei Provincial Key Laboratory of Neurological Diseases, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, PR China.
Liao
Xiao-Mei
XM
Chen
Xiao-Qian
XQ
Liu
Gong-Ping
GP
Wang
Jian-Zhi
JZ
D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D006801:Humans; D019319:Okadaic Acid / Q000494:pharmacology; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D061988:Proteasome Inhibitors; D016875:tau Proteins / Q000378:metabolism*
D015853:Cysteine Proteinase Inhibitors; D061988:Proteasome Inhibitors; D016875:tau Proteins; C067713:lactacystin; D005576:Colforsin; D019319:Okadaic Acid; D046988:Proteasome Endopeptidase Complex; D000111:Acetylcysteine