Regulation of Apoptosis by Caspases
Abstract
We identified LKBi, a Ser/Thr kinase in which mutations are responsible for Peutz-Jegher disease, is a substrate of caspase-8 in vitro. Peutz-Jegher syndrome is a rare autosomal dominant disease characterized by a predisposition to develop benign and malignant tumors of many tissue origins including breast cancers. We discovered that LKB 1 is a novel pro-apoptotic protein that mediates cell death in a p53-dependent manner. Furthermore, we showed that the endogenous LKB 1 protein is recruited to mitochondria upon induction of apoptosis. In normal small intestine, we found that the expression levels of LKB 1 are higher in the tip of villus and highly upregulated in the cytoplasm of isolated epithelial cells with pyknotic nuclei. In contrast, the small intestine of Peutz-Jegher patients showed mosaic expression of LKB 1 with much of the polyps lacking LKB 1 staining. Consistent with its role in regulation of apoptosis, we found a dramatic reduction of apoptotic cells in polyps of PJS patients. We propose that inhibition of apoptosis is one of the key factors responsible for the formation of multiple benign intestinal polyps in PJS and possibly for the development of malignant tumors as well.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2000
- Accession Number
- ADB266022
Entities
People
- Junying Yuan
Organizations
- Harvard University