Ping Zhang

Publications (3)19.11 Total impact

• Article: The HDAC inhibitor depsipeptide transactivates the p53/p21 pathway by inducing DNA damage.

  Haiying Wang, Wen Zhou, Zhixing Zheng, Ping Zhang, Bo Tu, Qihua He, Wei-Guo Zhu
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  ABSTRACT: Histone deacetylase (HDAC) inhibitors have been proven to be effective therapeutic agents to kill cancer cells through inhibiting HDAC activity or altering the structure of chromatin. As a potent HDAC inhibitor, depsipeptide not only modulates histone deacetylation but also activates non-histone protein p53 to inhibit cancer cell growth. However, the mechanism of depsipeptide-induced p53 transactivity remains unknown. Here, we show that depsipeptide causes DNA damage through induction of reactive oxygen species (ROS) generation, as demonstrated by a comet assay and by detection of the phosphorylation of H2AX. Depsipeptide induced oxidative stress was confirmed to relate to a disturbance in reduction-oxidation (redox) reactions through inhibition of the transactivation of thioredoxin reductase (TrxR) in human cancer cells. Upon treatment with depsipeptide, p53 phosphorylation at threonine 18 (Thr18) was specifically induced. Furthermore, we also demonstrated that phosphorylation of p53 at Thr18 is required for p53 acetylation at lysine 373/382 and for p21 expression in response to depsipeptide treatment. Our results demonstrate that depsipeptide plays an anti-neoplastic role by generating ROS to elicit p53/p21 pathway activation.
  DNA repair 11/2011; 11(2):146-56. · 4.20 Impact Factor
• Source

  Available from: Wei-Guo Zhu

  Article: Deficiency of hepatocystin induces autophagy through an mTOR-dependent pathway.

  Jing Yang, Ying Zhao, Ke Ma, Fen-Jun Jiang, Wenjuan Liao, Ping Zhang, Jingyi Zhou, Bo Tu, Lina Wang, Harm H Kampinga, Zhiping Xie, Wei-Guo Zhu
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  ABSTRACT: Mutations in the gene encoding hepatocystin/80K-H (PRKCSH) cause autosomal-dominant polycystic liver disease (ADPLD). Hepatocystin functions in the processing of nascent glycoproteins as the noncatalytic beta subunit of glucosidase II (Glu II) and regulates calcium release from endoplasmic reticulum (ER) through the inositol 1,4,5-trisphosphate receptor (IP3R). Little is known, however, on how cells respond to a deficiency of hepatocystin. In this study, we demonstrate that knockdown of hepatocystin induces autophagy, the major intracellular degradation pathway essential for cellular health. Ectopic expression of wild-type hepatocystin, but not pathogenic mutants, rescues the siRNA-induced effect. Our data indicate that the induction of autophagy by hepatocystin deficiency is mediated through mammalian target of rapamycin (mTOR). Despite the resulting severe reduction in Glu II activity, the unfolded protein response (UPR) pathway is not disturbed. Furthermore, the inhibition of IP3R-mediated transient calcium flux is not required for the induction of autophagy. These results provide new insights into the function of hepatocysin and the regulation of autophagy.
  Autophagy 07/2011; 7(7):748-59. · 7.45 Impact Factor
• Source

  Available from: Wei-Guo Zhu

  Article: Anti-neoplastic activity of the cytosolic FoxO1 results from autophagic cell death.

  Ying Zhao, Lina Wang, Jing Yang, Ping Zhang, Ke Ma, Jingyi Zhou, Wenjuan Liao, Wei-Guo Zhu
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  ABSTRACT: Although Beclin 1 and mTOR are considered to be the main molecules to modulate the autophagic process, searching for other autophagy-regulating molecules is still an ongoing challenge to scientists. Here we demonstrated that FoxO1, a forkhead O family protein, is a mediator of autophagy. Upon oxidative stress or serum starvation, endogenous FoxO1 was required for autophagy in human cancer cell lines, and this process was independent of FoxO1's transcriptional activity as well as mTOR or Beclin 1. In response to stress, FoxO1 dissociated from an NAD(+)-dependent histone deacetylase SIRT2 and FoxO1 thus became acetylated and in turn bound to Atg7, an E1-like protein, to influence the autophagic process leading to cell death. In particular, cytosolic FoxO1 suppressed tumor xenograft growth in nude mice in an autophagy-dependent manner. Our studies provide evidence that cytosolic FoxO1-induced autophagy is associated with tumor suppression function.
  Autophagy 10/2010; 6(7):988-90. · 7.45 Impact Factor