Regulation of polyamine homeostasis through an antizyme citrullination pathway
| العنوان: | Regulation of polyamine homeostasis through an antizyme citrullination pathway |
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| المؤلفون: | Chien-Yun Lee, Hui-Chih Hung, Chi-Li Lin, Ju-Yi Hsieh, Yi-Liang Liu, Guang-Yaw Liu, Yi-Fang Yang |
| المصدر: | Journal of Cellular Physiology. 236:5646-5663 |
| بيانات النشر: | Wiley, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Proteasome Endopeptidase Complex, genetic structures, Physiology, Clinical Biochemistry, Cell, Ornithine Decarboxylase, Protein citrullination, Ornithine decarboxylase, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Polyamines, medicine, Homeostasis, Humans, Ornithine decarboxylase antizyme, Chemistry, fungi, Citrullination, Cell Biology, Ornithine Decarboxylase Inhibitors, Cell biology, 030104 developmental biology, medicine.anatomical_structure, Proteasome, 030220 oncology & carcinogenesis, Putrescine, Polyamine homeostasis, Carrier Proteins |
| الوصف: | This study reveals an uncovered mechanism for the regulation of polyamine homeostasis through protein arginyl citrullination of antizyme (AZ), a natural inhibitor of ornithine decarboxylase (ODC). ODC is critical for the cellular production of polyamines. AZ binds to ODC dimers and promotes the degradation of ODC via the 26S proteasome. This study demonstrates the protein citrullination of AZ catalyzed by peptidylarginine deiminase type 4 (PAD4) both in vitro and in cells. Upon PAD4 activation, the AZ protein was citrullinated and accumulated, leading to higher levels of ODC proteins in the cell. In the PAD4-overexpressing and activating cells, the levels of ODC enzyme activity and the product putrescine increased with the level of citrullinated AZ proteins and PAD4 activity. Suppressing cellular PAD4 activity reduces the cellular levels of ODC and downregulates cellular polyamines. Furthermore, citrullination of AZ in the C-terminus attenuates AZ function in the inhibition, binding, and degradation of ODC. This paper provides evidence to illustrate that PAD4-mediated AZ citrullination upregulates cellular ODC and polyamines by retarding ODC degradation, thus interfering with the homeostasis of cellular polyamines, which may be an important pathway regulating AZ functions that is relevant to cancer biology. |
| تدمد: | 1097-4652 0021-9541 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f39d58758fb78d9a0ef06f4107825139Test https://doi.org/10.1002/jcp.30252Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....f39d58758fb78d9a0ef06f4107825139 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10974652 00219541 |
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