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P3‐315: Inhibition of gamma‐secretase activity induces cell cycle defects and chromosome missegregation
Author(s) -
Goodwin Bonnie,
Padmanabhan Jaya,
Granic Antoneta,
Owens Caroline,
Crespo Nicole,
Potter Huntington
Publication year - 2008
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2008.05.1884
Subject(s) - amyloid precursor protein , cell cycle , biology , neurodegeneration , presenilin , microbiology and biotechnology , population , alzheimer's disease , chemistry , cancer research , cell , pathology , medicine , genetics , disease , environmental health
the activity of protein phosphatase-2A through increasing the level of inhibitor-2 of protein phosphatase-2A (I2 ). A growing number of evidence indicate that the protein I2 PP-2A is a key regulator of several cellular processes including cell cycle control, chromatin remodeling, apoptosis, cell signaling, neuronal development, and RNA metabolism. Moreover it also plays a role in transcriptional regulation. Objective: In the present study we identified genes which could be positively regulated by I2 PP-2A and its potential role on HEK293 cells. Methods: pSupper-si I2 PP-2A plasmid was constructed for knock-down the level of I2 . pSUP-si I2 PP-2A or pcDNA-I2 PP-2A was transiently transfected into HEK293 cells respectively and the mRNA and protein levels of p53 were detected by western blots and real-time PCR. The promoter activity was measured by chromatin immunoprecipitation (CHIP) and luciferase assay. Flow cytometer was used to analysis apoptosis and cell cycle. Results: We found that knockdown of I2 PP-2A decreased the mRNA and protein levels of p53, whereas overexpression of I2 PP-2A increased the levels of p53. And manipulation of PP-2A activity by overexpressing PP-2A plasmids did not affect the level of p53. We also found that I2 PP-2A protein could increase the activity of p53 promoter. Overexpression of I2 PP-2A increased the immunostaining of phospho-p53 (Ser 46), however did not increase the rate of apoptosis. Conclusions: I2 PP-2A may regulate p53 in transcription level and thus affect the cell cycle.