The influence of differential processing of procathepsin H on its aminopeptidase activity, secretion and subcellular localization in human cell lines
Rojnik, Matija (Author), Jevnikar, Zala (Author), Doljak, Bojan (Author), Turk, Samo (Author), Zidar, Nace (Author), Kos, Janko (Author)

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Cathepsin H is a unique member of the cysteine cathepsins that acts primarily as an aminopeptidase. Like other cysteine cathepsins, it is synthesized as an inactive precursor and activated by proteolytic removal of its propeptide. Here we demonstrate that, in human cells, the processing of the propeptide is an autocatalytic, multistep process proceeding from an inactive 41 kDa pro-form, through a 30 kDa intermediate form, to the 28 kDa mature form. Tyr87P and Gly90P were identified as the two major endopeptidase cleavage sites, converting the 30 kDa form into the mature 28 kDa form. The level of processing differs significantly in different human cell lines. In monocyte-derived macrophages U937 and prostate cancer cells PC-3, the 28 kDa form is predominant, whereas in osteoblasts HOS the processing from the 30 kDaform to the 28 kDa form is significantly lower. The aminopeptidase activityof the enzyme and its subcellular localization are independent of the product, however the 30 kDa form was not secreted in HOS cells. The activity of the resulting cathepsin H in U937 cells was significantly lower than that in HOS cells, presumably due to the high levels of endogenous cysteine protease inhibitor cystatin F present specifically in this cell line. These results provide an insight into the dependence of human cathepsin H processingand regulation on cell type.

Keywords:katepsin H, celične linije, encimi, rak
Work type:Not categorized (r6)
Tipology:1.01 - Original Scientific Article
Organization:FFA - Faculty of Pharmacy
Number of pages:str. 757-764
Numbering:Vol. 91, iss. 10
ISSN on article:0171-9335
DOI:10.1016/j.ejcb.2012.05.004 Link is opened in a new window
COBISS.SI-ID:3269745 Link is opened in a new window
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Record is a part of a journal

Title:European journal of cell biology
Shortened title:Eur. j. cell biol.
Publisher:Elsevier, Urban u. Fischer
COBISS.SI-ID:25426688 This link opens in a new window

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