Impact of Reactive Oxygen and Nitrogen Species Produced by Plasma on Mdm2–p53 Complex

The study of protein–protein interactions is of great interest. Several early studies focused on the murine double minute 2 (Mdm2)–tumor suppressor protein p53 interactions. However, the effect of plasma treatment on Mdm2 and p53 is still absent from the literature. This study investigated the structural changes in Mdm2, p53, and the Mdm2–p53 complex before and after possible plasma oxidation through molecular dynamic (MD) simulations. MD calculation revealed that the oxidized Mdm2 bounded or unbounded showed high flexibility that might increase the availability of tumor suppressor protein p53 in plasma-treated cells. This study provides insight into Mdm2 and p53 for a better understanding of plasma oncology.

DNA damage and necroptosis induced by peroxidase from proso millet in human colorectal cancer cells

Purpose: To investigate the effects of cationic peroxidase from proso millet (PmPOD) on DNA damage and necroptosis in human colon cancer HCT116 and HT29 cells. Methods: Cell necroptosis and cell cycle was stained using Annexin V-FITC and cell cycle kits, respectively, and evaluated by flow cytometry. Lipid raft on the membrane was disrupted by cholesterol depletion and the location of PmPOD observed by confocal microscopy. Comet assays were used to detect DNA damage, and different inhibitors were also used. Knockdown of p53 or ectopic p53 expression in HCT116 cells were transfected p53 siRNA and pCMV3-TP53-myc plasmid, and p53 expression analyzed by western blotting. Results: Pre-treatment of HCT116 and HT29 cell lines with the specific necroptosis inhibitor Nec-1 prevented PmPOD-induced necroptosis, whereas the apoptosis inhibitor, z-VAD-fmk, had no effect. The entry of PmPOD is necessary for induction of DNA damage and necroptosis. Furthermore, PmPOD induced cell cycle arrest at S phase, as well as DNA DSBs in vivo, as reflected by numerous γ-H2AX foci in CRC cells. However, the tumor suppressor protein, p53, alleviated PmPOD-induced DNA damage and necroptosis. Conclusions: These results demonstrate that PmPOD-induced DNA DSBs in CRC cells is the main cause of necroptosis, and that the tumor suppressor protein, p53, alleviates PmPOD-induced necroptosis by promoting p53-mediated repair pathways.

Recent Advances in p53

Tumor suppressor protein p53 (TP53) is a key transcription factor that, in response to various stress signals, regulates numerous genes involved in a broad range of cellular functions including DNA repair, apoptosis, cell cycle arrest, senescence, metabolism, etc [...]

Semisynthetic ‘designer’ p53 sheds light on a phosphorylation-acetylation relay

The tumor suppressor protein p53 is a master regulator of cell fate. The activity of p53 is controlled by a plethora of posttranslational modifications (PTMs). However, despite extensive research, the...