Protein processing by the placental protease, cathepsin P

Cathepsin P is a member of a family of placentally expressed cathepsins (PECs). The closest human homolog of cathepsin P is cathepsin L, a broad specificity enzyme that has functions in many tissues in addition to placenta. The gene duplications that gave rise to the PECs provide a rare opportunity...

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Bibliographic Details
Published in:Molecular human reproduction 2009-07, Vol.15 (7), p.433-442
Main Authors: Hassanein, M., Bojja, A. Sri, Glazewski, L., Lu, G., Mason, R.W.
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Blotting, Western
Calreticulin - metabolism
Calreticulin - pharmacology
cathepsin
Cathepsins - metabolism
Cell Differentiation - drug effects
Cell Line, Tumor
Electrophoresis, Gel, Two-Dimensional
Embryology: invertebrates and vertebrates. Teratology
Female
Fundamental and applied biological sciences. Psychology
Immunohistochemistry
placenta
Placenta - enzymology
processing
proteolysis
Rats
Trophoblasts - cytology
Trophoblasts - drug effects
Trophoblasts - metabolism
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Summary:Cathepsin P is a member of a family of placentally expressed cathepsins (PECs). The closest human homolog of cathepsin P is cathepsin L, a broad specificity enzyme that has functions in many tissues in addition to placenta. The gene duplications that gave rise to the PECs provide a rare opportunity to define proteolytic functions in placenta, a transient organ unique to mammals. Peptidyl substrate and inhibitor libraries have shown that cathepsin P has evolved an unusually restricted preference for substrates containing hydrophobic amino acids. Proteomic techniques were used to probe for substrates of this enzyme. Recombinant cathepsin P was incubated with rat choriocarcinoma (Rcho-1) cell proteins to identify substrates using two-dimensional difference gel electrophoresis. Substrate proteins were excised from gels and characterized by trypsin digestion and MALDI MS/MS. Two endoplasmic reticulum (ER) proteins, gp96 and calreticulin, emerged as potential substrates, and western blotting showed that these proteins are processed by cathepsin P from their C-terminus, removing the KDEL ER retention signal. Immunohistochemistry showed that a portion of cathepsin P co-localizes with calreticulin in Rcho-1 cells. Extracellular calreticulin induces differentiation of Rcho-1 cells, indicating a potential role of cathepsin P in processing and secretion of calreticulin during differentiation of trophoblast giant cells.
ISSN:1360-9947
1460-2407
DOI:10.1093/molehr/gap029