Acetylation‐mediated Siah2 stabilization enhances PHD3 degradation in Helicobacter pylori‐infected gastric epithelial cancer cells
| Autor: | Shivaram Prasad Singh, Suvasmita Rath, Shrikant Babanrao Kokate, Arjama Dhar Roy, Asima Bhattacharyya, Pragyesh Dixit, Indrajit Poirah, Lopamudra Das, Debashish Chakraborty, Niranjan Rout |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Ubiquitin-Protein Ligases SIAH2 Biochemistry Helicobacter Infections Hypoxia-Inducible Factor-Proline Dioxygenases 03 medical and health sciences Stomach Neoplasms Cell Line Tumor Enzyme Stability Genetics medicine Humans Helicobacter Molecular Biology Helicobacter pylori biology Chemistry Nuclear Proteins Cancer Acetylation Epithelial Cells biology.organism_classification medicine.disease Neoplasm Proteins Ubiquitin ligase 030104 developmental biology Hypoxia-inducible factors Gastric Mucosa Proteolysis Cancer cell biology.protein Cancer research Biotechnology |
| Zdroj: | The FASEB Journal. 32:5378-5389 |
| ISSN: | 1530-6860 0892-6638 |
| Popis: | Gastric epithelial cells infected with Helicobacter pylori acquire highly invasive and metastatic characteristics. The seven in absentia homolog (Siah)2, an E3 ubiquitin ligase, is one of the major proteins that induces invasiveness of infected gastric epithelial cells. We find that p300-driven acetylation of Siah2 at lysine 139 residue stabilizes the molecule in infected cells, thereby substantially increasing its efficiency to degrade prolyl hydroxylase (PHD)3 in the gastric epithelium. This enhances the accumulation of an oncogenic transcription factor hypoxia-inducible factor 1α (Hif1α) in H. pylori-infected gastric cancer cells in normoxic condition and promotes invasiveness of infected cells. Increased acetylation of Siah2, Hif1α accumulation, and the absence of PHD3 in the infected human gastric metastatic cancer biopsy samples and in invasive murine gastric cancer tissues further confirm that the acetylated Siah2 (ac-Siah2)-Hif1α axis is crucial in promoting gastric cancer invasiveness. This study establishes the importance of a previously unrecognized function of ac-Siah2 in regulating invasiveness of H. pylori-infected gastric epithelial cells.-Kokate, S. B., Dixit, P., Das, L., Rath, S., Roy, A. D., Poirah, I., Chakraborty, D., Rout, N., Singh, S. P., Bhattacharyya, A. Acetylation-mediated Siah2 stabilization enhances PHD3 degradation in Helicobacter pylori-infected gastric epithelial cancer cells. |
| Databáze: | OpenAIRE |
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