Poly-ADP-ribosylation of HMGB1 regulates TNFSF10/TRAIL resistance through autophagy

Minghua Yang, Liying Liu, Min Xie, Xiaofang Sun, Yan Yu, Rui Kang, Liangchun Yang, Shan Zhu, Lizhi Cao, Daolin Tang

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)214-224
Number of pages11
JournalAutophagy
Volume11
Issue number2
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

Fingerprint

Autophagy
Adenosine Diphosphate
Apoptosis
Cell Death
TNF-Related Apoptosis-Inducing Ligand
Neoplasms
Nuclear Proteins
Eating
Poly (ADP-Ribose) Polymerase-1
Pharmacology
Gene Expression
Pharmaceutical Preparations

Keywords

  • Apoptosis
  • Autophagy
  • HMGB1
  • PARP-1
  • TRAIL

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Poly-ADP-ribosylation of HMGB1 regulates TNFSF10/TRAIL resistance through autophagy. / Yang, Minghua; Liu, Liying; Xie, Min; Sun, Xiaofang; Yu, Yan; Kang, Rui; Yang, Liangchun; Zhu, Shan; Cao, Lizhi; Tang, Daolin.

In: Autophagy, Vol. 11, No. 2, 01.01.2015, p. 214-224.

Research output: Contribution to journalArticle

Yang, M, Liu, L, Xie, M, Sun, X, Yu, Y, Kang, R, Yang, L, Zhu, S, Cao, L & Tang, D 2015, 'Poly-ADP-ribosylation of HMGB1 regulates TNFSF10/TRAIL resistance through autophagy', Autophagy, vol. 11, no. 2, pp. 214-224. https://doi.org/10.4161/15548627.2014.994400
Yang, Minghua ; Liu, Liying ; Xie, Min ; Sun, Xiaofang ; Yu, Yan ; Kang, Rui ; Yang, Liangchun ; Zhu, Shan ; Cao, Lizhi ; Tang, Daolin. / Poly-ADP-ribosylation of HMGB1 regulates TNFSF10/TRAIL resistance through autophagy. In: Autophagy. 2015 ; Vol. 11, No. 2. pp. 214-224.
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