The Significance of Cathepsin V and its N-terminally Truncated Form in Thyroid Physiology and Carcinogenesis

  • As cell biologists and specialized in proteases, our group has made significant contributions to the understanding of the role of cathepsins, in the maintenance of thyroid function. In this study, we examined the significance of cathepsin V in thyroid physiology and carcinogenesis. Immunofluorescence analysis of non-cancerous and cancerous human thyroid tissue showed the localization of cathepsin V at the apical plasma membrane domain of thyrocytes and within the follicle lumen of normal thyroid tissue, whereas cathepsin V was found within nuclei in cells of follicular and papillary thyroid carcinoma tissue. These results prompted us to explore which molecular form of cathepsin V can be secreted and/or sorted to the nuclear compartment of thyrocytes. To this end, we created two cell lines stably expressing full-length (hCV-eGFP) and N-terminally truncated cathepsin V (h56NCV-eGFP), both tagged with eGFP at their C-termini, which are referred to as Nthyori-CV and Nthyori-NCV, respectively. We found that hCV-eGFP chimeric protein follows the canonical transport pathway of cathepsins from the rough endoplasmic reticulum (ER) lumen through the Golgi apparatus to endo-lysosomes. In addition, our results revealed that Nthyori-CV cells secrete the proform of the hCV-eGFP chimeric protein in a TSH-regulated pattern into the extracellular space. On the other hand, h56NCV-eGFP chimeric protein which lacks the ER lumen-targeting signal peptide and part of the propeptide escaped the secretory pathway, which explains its unusual presence in the cytosol and accumulation in the nuclei of Nthyori-NCV cells. In particular, it was more abundant in the nuclei during S phase, suggesting that nuclear cathepsin V might be involved in the regulation of cell cycle progression of thyrocytes. Thus, we investigated the effect of h56NCV-eGFP expression on the proliferation rate of thyrocytes. We found that Nthyori-NCV cells are more proliferative than both Nthyori-CV and wild-type controls.

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Publishing Institution:IRC-Library, Information Resource Center der Jacobs University Bremen
Granting Institution:Jacobs Univ.
Author:Alaa Al-Hashimi
Referee:Klaudia Brix, Matthias Ullrich, Bonnie F. Sloane
Advisor:Klaudia Brix
Persistent Identifier (URN):urn:nbn:de:gbv:579-opus-1010162
Document Type:PhD Thesis
Date of Successful Oral Defense:2021/07/12
Date of First Publication:2022/01/17
Academic Department:Life Sciences & Chemistry
PhD Degree:Cell Biology
Focus Area:Health
Other Countries Involved:United States of America
Call No:2021/19

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