Poly-ADP-ribosylation of HMGB1 regulates TNFSF10/TRAIL resistance through autophagy
| Autor: | Yan Yu, Min Xie, Liangchun Yang, Lizhi Cao, Liying Liu, Shan Zhu, Xiaofang Sun, Daolin Tang, Rui Kang, Minghua Yang |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Programmed cell death
Poly (ADP-Ribose) Polymerase-1 Regulator Apoptosis chemical and pharmacologic phenomena Basic Science Research Papers HMGB1 TNF-Related Apoptosis-Inducing Ligand Mice PARP1 Cell Line Tumor Autophagy Animals Humans HMGB1 Protein Nuclear protein Molecular Biology biology Cell Biology Molecular biology Cell biology Cancer cell biology.protein Poly(ADP-ribose) Polymerases Apoptosis Regulatory Proteins Signal Transduction |
| Zdroj: | Autophagy. 11:214-224 |
| ISSN: | 1554-8635 1554-8627 |
| DOI: | 10.4161/15548627.2014.994400 |
| Popis: | Both apoptosis ("self-killing") and autophagy ("self-eating") are evolutionarily conserved processes, and their crosstalk influences anticancer drug sensitivity and cell death. However, the underlying mechanism remains unclear. Here, we demonstrated that HMGB1 (high mobility group box 1), normally a nuclear protein, is a crucial regulator of TNFSF10/TRAIL (tumor necrosis factor [ligand] superfamily, member 10)-induced cancer cell death. Activation of PARP1 (poly [ADP-ribose] polymerase 1) was required for TNFSF10-induced ADP-ribosylation of HMGB1 in cancer cells. Moreover, pharmacological inhibition of PARP1 activity or knockdown of PARP1 gene expression significantly inhibited TNFSF10-induced HMGB1 cytoplasmic translocation and subsequent HMGB1-BECN1 complex formation. Furthermore, suppression of the PARP1-HMGB1 pathway diminished autophagy, increased apoptosis, and enhanced the anticancer activity of TNFSF10 in vitro and in a subcutaneous tumor model. These results indicate that PARP1 acts as a prominent upstream regulator of HMGB1-mediated autophagy and maintains a homeostatic balance between apoptosis and autophagy, which provides new insight into the mechanism of TNFSF10 resistance. |
| Databáze: | OpenAIRE |
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