Inhibitors of protein phosphatase-2A from human brain structures, immunocytological localization and activities towards dephosphorylation of the Alzheimer type hyperphosphorylated tau

Autor:	Jiliu Xu, Khalid Iqbal, Ichiro Tsujio, Leszek Kotula, Inge Grundke-Iqbal, Tanweer Zaidi
Rok vydání:	2004
Předmět:	Chromosomal Proteins Non-Histone PHAP Gene Expression PC12 Cells environment and public health Biochemistry Mice 0302 clinical medicine Structural Biology Phosphoprotein Phosphatases Protein Phosphatase 2 Phosphorylation Neurons 0303 health sciences Stem Cells Intracellular Signaling Peptides and Proteins Brain Nuclear Proteins RNA-Binding Proteins Transfection 3. Good health DNA-Binding Proteins medicine.anatomical_structure embryonic structures Alzheimer disease Microtubule-associated protein Recombinant Fusion Proteins Green Fluorescent Proteins Molecular Sequence Data Phosphatase Biophysics tau Proteins macromolecular substances Biology Dephosphorylation 03 medical and health sciences Genetics medicine Animals Humans Histone Chaperones Amino Acid Sequence RNA Messenger Molecular Biology 030304 developmental biology Brain Chemistry Cell Nucleus Template activating factor Protein phosphatase-2A inhibitor Proteins Cell Biology Protein phosphatase 2 Molecular biology Rats enzymes and coenzymes (carbohydrates) Cell nucleus Cytoplasm LANP NIH 3T3 Cells Abnormally hyperphosphorylated tau 030217 neurology & neurosurgery Transcription Factors
Zdroj:	FEBS Letters. 579:363-372
ISSN:	0014-5793
DOI:	10.1016/j.febslet.2004.11.097
Popis:	Protein phosphatase (PP)-2A, which regulates the phosphorylation of tau, is regulated by two endogenous inhibitor proteins, I(1)(PP2A) and I(2)(PP2A), in mammalian tissues. Here, we report the cloning of I(1)(PP2A) and I(2)(PP2A) from human brain, and show that in PC12 cells and in I(1)(PP2A)-GFP or I(2)(PP2A)-GFP transfected NIH3T3 and human neural progenitor cells, I(1)(PP2A) is localized mostly in the cell cytoplasm and I(2)(PP2A) mostly in the nucleus. The recombinant I(1)(PP-2A) and I(2)(PP-2A) inhibit PP-2A activity towards hyperphosphorylated tau in vitro; the dephosphorylation of the hyperphosphorylated tau at specific sites is selectively inhibited. Overexpression of I(1)(PP2A) as well as I(2)(PP2A) results in tau hyperphosphorylation and degeneration of PC 12 cells.
Databáze:	OpenAIRE
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