Cystatin C as a p53-inducible apoptotic mediator that regulates cathepsin L activity.
Bottom Line: We showed that cathepsin L activity was decreased in HCT116 p53(+/+) cells after adriamycin treatment, but not in HCT116 p53(-/-) cells.We also found that knockdown of cystatin C reduced adriamycin-induced caspase-3 activation.Cystatin C expression was significantly downregulated in breast cancer cells with p53 mutations, and decreased cystatin C expression was associated with poor prognosis of breast cancer.
Affiliation: Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Minato, Tokyo, Japan.Show MeSH
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Mentions: To investigate whether cystatin C is a direct target of p53, we surveyed for the p53 binding sequence35 within the cystatin C locus and identified a potential binding site (p53BS) in the first intron (Fig. 3a). A 263‐base DNA fragment containing p53BS was amplified and subcloned upstream of the minimal promoter in pGL4.24 vector (pGL4.24/p53BS). The result of reporter assay revealed that U373MG cells transfected with pGL4.24/p53BS showed increased luciferase activity only in the presence of plasmid expressing wild‐type p53 (Fig. 3b). However, base substitutions in p53BS (pGL4.24/p53BSmut) diminished the enhancement of luciferase activity.
Affiliation: Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Minato, Tokyo, Japan.