title: Mechanism of inhibition of PP2A activity and abnormal hyperphosphorylation of tau by I2(PP2A)/SET.
abstract: Protein phosphatase-2A (PP2A) activity, which is compromised in Alzheimer disease brain, is regulated by two endogenous inhibitors, one of them being I(2)(PP2A), a 277 amino acid long protein also known as SET. Here we report that both the amino terminal fragment (I(2NTF); aa 1-175) and the carboxy terminal fragment (I(2CTF); aa 176-277) of I(2)(PP2A) inhibit PP2A by binding to its catalytic subunit PP2Ac and cause hyperphosphorylation of tau. The C-terminal acidic region in I(2CTF) and Val 92 in I(2NTF) are essential for their association with PP2Ac and inhibition of the phosphatase activity.
authors.affiliation: Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USA.
authors.forename: Lisette
authors.initials: L
authors.lastname: Arnaud
authors.forename: She
authors.initials: S
authors.lastname: Chen
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.forename: Sabiha
authors.initials: S
authors.lastname: Khatoon
authors.forename: Inge
authors.initials: I
authors.lastname: Grundke-Iqbal
authors.forename: Khalid
authors.initials: K
authors.lastname: Iqbal
mesh_terms: D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins; D056488:Histone Chaperones / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D010766:Phosphorylation; D011485:Protein Binding; D054648:Protein Phosphatase 2 / Q000378:metabolism*; D021122:Protein Subunits; D014157:Transcription Factors / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D056488:Histone Chaperones; D021122:Protein Subunits; C513473:SET protein, human; D014157:Transcription Factors; D016875:tau Proteins; D054648:Protein Phosphatase 2