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In vitro study of proteolytic degradation of rat histidine decarboxylase
- Olmo, MarÃa T., Urdiales, JosÃ© L., Pegg, Anthony E., Medina, Miguel A., SÃ¡nchezâJimÃ©nez, Francisca
- European journal of biochemistry 2000 v.267 no.5 pp. 1527-1531
- histidine decarboxylase, in vitro studies, ornithine decarboxylase, proteasome endopeptidase complex, protein degradation, proteolysis, rats, regulatory proteins
- Mammalian ornithine decarboxylase (ODC) is a very unstable protein which is degraded in an ATPâdependent manner by proteasome 26S, after making contact with the regulatory protein antizyme. PEST regions are sequences described as signals for protein degradation. The Câterminal PEST region of mammalian ODC is essential for its degradation by proteasome 26S. Mammalian histidine decarboxylase (HDC) is also a shortâlived protein. The full primary sequence of mammalian HDC contains PESTâregions at both the Nâ and Câtermini. Rat ODC and different truncated and full versions of rat HDC were expressed in vitro. In vitro degradation of rat ODC and rat 1â512 HDC were compared. Like ODC, rat 1â512 HDC is degraded mainly by an ATPâdependent mechanism. However, antizyme has no effect on the degradation of 1â512 HDC. The use of the inhibitors MGâ132 and lactacystine significantly inhibited the degradation of 1â512 HDC, suggesting that a ubiquitinâdependent, proteasome 26S proteolytic pathway is involved. Results obtained with the different modifications of rat HDC containing all three PEST regions (full version, 1â656 HDC), only the Nâterminal PEST region (1â512 HDC), or no PEST region (69â512 HDC), indicate that the Nâterminal (1â69) fragment, but not the Câterminal fragment, determines that the HDC protein is a proteasome substrate in vitro.