Tubulin couples death receptor 5 to regulate apoptosis
| Autor: | Julianne D. Twomey, Qing Xu, Liqun Zhao, Shen Luo, Baolin Zhang |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
biology Chemistry apoptosis TRAIL Ligand (biochemistry) Cell biology Recombinant tumor necrosis factor 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Tubulin tubulin Oncology Microtubule Apoptosis 030220 oncology & carcinogenesis Cancer cell biology.protein cancer therapy Gene silencing death receptor 5 Tumor necrosis factor alpha Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.26407 |
| Popis: | Activation of death receptor 5 (DR5) to induce apoptosis in cancer cells is an attractive strategy for cancer therapy. However, many tumor cell lines and primary tumors are resistant to DR5 targeted agents including recombinant tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and anti-DR5 agonistic antibodies. Here we identify tubulin proteins - primarily consisting of α and β subunits folded into microtubule polymers - as a crucial modulator of DR5 mediated apoptosis. Using affinity purification coupled with mass spectrometry, we found that DR5 interacts with both α- and β-tubulin proteins in cancer cells. Pharmacological disruption of microtubules increased DR5 protein expression and subsequently sensitized the cells to TRAIL-induced apoptosis. Similar results were observed by selectively silencing tubulin transcript using small RNA interference. We also demonstrate that tubulin/microtubule blockade augments TRAIL induced apoptosis by stabilizing DR5 protein. Together, our results link the tubulin/microtubule network to the stringent regulation of DR5 mediated apoptosis, which could lead to potential therapeutic strategies to enhance cancer therapy efficacy. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|