A nuclear protein tyrosine phosphatase activates p53 and induces caspase-1-dependent apoptosis.
PTP-S2/TC45 is a nuclear protein tyrosine phosphatase, which induces p53-dependent apoptosis. Here we show that the p53 protein level increased in MCF-7 cells in response to PTP-S2 overexpression. PTP-S2-induced p53 protein was transcriptionally active and it could activate caspase-1 gene expression from endogenous as well as ectopic promoter. Coexpression of an active site mutant of procaspase-1 strongly inhibited PTP-S2-induced apoptosis. Mutant procaspase-1 also inhibited apoptosis induced by p53 overexpression or doxorubicin treatment, which induce caspase-1 gene expression. In contrast, apoptosis induced by staurosporine or cycloheximide, which do not increase caspase-1 gene expression, was not affected by mutant procaspase-1. These results suggest that caspase-1 may be one of the mediators of p53-dependent apoptosis in human cells.
Gupta
Sanjeev
S
Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007, India.
Radha
Vegesna
V
Sudhakar
Ch
Ch
Swarup
Ghanshyam
G
D017209:Apoptosis; D020170:Caspase 1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D009687:Nuclear Proteins / Q000502:physiology*; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D009687:Nuclear Proteins; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; C516649:PTPN2 protein, human; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2; D017027:Protein Tyrosine Phosphatases; D020170:Caspase 1