Nuclear cysteine cathepsin variants in thyroid carcinoma cells
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Sofia Tedelind
Abstract
The cysteine peptidase cathepsin B is important in thyroid physiology by being involved in thyroid prohormone processing initiated in the follicular lumen and completed in endo-lysosomal compartments. However, cathepsin B has also been localized to the extrafollicular space and is therefore suggested to promote invasiveness and metastasis in thyroid carcinomas through, e.g., ECM degradation. In this study, immunofluorescence and biochemical data from subcellular fractionation revealed that cathepsin B, in its single- and two-chain forms, is localized to endo-lysosomes in the papillary thyroid carcinoma cell line KTC-1 and in the anaplastic thyroid carcinoma cell lines HTh7 and HTh74. This distribution is not affected by thyroid stimulating hormone (TSH) incubation of HTh74, the only cell line that expresses a functional TSH-receptor. Immunofluorescence data disclosed an additional nuclear localization of cathepsin B immunoreactivity. This was supported by biochemical data showing a proteolytically active variant slightly smaller than the cathepsin B proform in nuclear fractions. We also demonstrate that immunoreactions specific for cathepsin V, but not cathepsin L, are localized to the nucleus in HTh74 in peri-nucleolar patterns. As deduced from co-localization studies and in vitro degradation assays, we suggest that nuclear variants of cathepsins are involved in the development of thyroid malignancies through modification of DNA-associated proteins.
©2010 by Walter de Gruyter Berlin New York
Articles in the same Issue
- Guest Editorial
- Highlight: The Biology of Proteolytic Systems
- Highlight: 6th General Meeting of the International Proteolysis Society
- Structure, mechanism and inhibition of γ-secretase and presenilin-like proteases
- Is BACE1 a suitable therapeutic target for the treatment of Alzheimer's disease? Current strategies and future directions
- Pharmacogenetic features of cathepsin B inhibitors that improve memory deficit and reduce β-amyloid related to Alzheimer's disease
- Proteases in lymphocyte killer function: redundancy, polymorphism and questions remaining
- Pseudo-active sites of protease domains: HGF/Met and Sonic hedgehog signaling in cancer
- Proteolysis of platelet receptors in humans and other species
- Blunting the knife: development of vaccines targeting digestive proteases of blood-feeding helminth parasites
- Impaired turnover of autophagolysosomes in cathepsin L deficiency
- Nuclear cysteine cathepsin variants in thyroid carcinoma cells
- Deletion of cathepsin H perturbs angiogenic switching, vascularization and growth of tumors in a mouse model of pancreatic islet cell cancer
- Cathepsin E enhances anticancer activity of doxorubicin on human prostate cancer cells showing resistance to TRAIL-mediated apoptosis
- Hydrophilic residues surrounding the S1 and S2 pockets contribute to dimerisation and catalysis in human dipeptidyl peptidase 8 (DP8)
- Molecular contortionism – on the physical limits of serpin ‘loop-sheet’ polymers
- The substrate specificity profile of human granzyme A
- Use of granzyme B-based fluorescent protein reporters to monitor granzyme distribution and granule integrity in live cells
Articles in the same Issue
- Guest Editorial
- Highlight: The Biology of Proteolytic Systems
- Highlight: 6th General Meeting of the International Proteolysis Society
- Structure, mechanism and inhibition of γ-secretase and presenilin-like proteases
- Is BACE1 a suitable therapeutic target for the treatment of Alzheimer's disease? Current strategies and future directions
- Pharmacogenetic features of cathepsin B inhibitors that improve memory deficit and reduce β-amyloid related to Alzheimer's disease
- Proteases in lymphocyte killer function: redundancy, polymorphism and questions remaining
- Pseudo-active sites of protease domains: HGF/Met and Sonic hedgehog signaling in cancer
- Proteolysis of platelet receptors in humans and other species
- Blunting the knife: development of vaccines targeting digestive proteases of blood-feeding helminth parasites
- Impaired turnover of autophagolysosomes in cathepsin L deficiency
- Nuclear cysteine cathepsin variants in thyroid carcinoma cells
- Deletion of cathepsin H perturbs angiogenic switching, vascularization and growth of tumors in a mouse model of pancreatic islet cell cancer
- Cathepsin E enhances anticancer activity of doxorubicin on human prostate cancer cells showing resistance to TRAIL-mediated apoptosis
- Hydrophilic residues surrounding the S1 and S2 pockets contribute to dimerisation and catalysis in human dipeptidyl peptidase 8 (DP8)
- Molecular contortionism – on the physical limits of serpin ‘loop-sheet’ polymers
- The substrate specificity profile of human granzyme A
- Use of granzyme B-based fluorescent protein reporters to monitor granzyme distribution and granule integrity in live cells
