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Summary: This article investigates the mechanistic aspects of mutant p53 “gain of function” in response to DNA damage. We show that mutant forms of p53 protein interact with NF-Y. The expression of cyclin A, cyclin B1, cdk1, and cdc25C, as well as the cdk1-associated kinase activities, is upregulated after DNA damage, provoking a mutant p53/NF-Y-dependent increase in DNA synthesis. Mutant p53 binds NF-Y target promoters and, upon DNA damage, recruits p300, leading to histone acetylation. The recruitment of mutant p53 to the CCAAT sites is severely impaired upon abrogation of NF-YA expression. Endogenous NF-Y, mutant p53, and p300 proteins form a triple complex upon DNA damage. We demonstrate that aberrant transcriptional regulation underlies the ability of mutant p53 proteins to act as oncogenic factors. [Copyright &y& Elsevier]

The aim was to study the shelf-life over 18 months of storage (no light and oxygen exposure) of chili peppers flavoured olive oils comparing flavouring methods of co-milling of fresh chili peppers with sound olives at mill scale with temporary and permanent infusion of dried chili peppers in olive oil. Tocopherols, secoiridoids and capsaicinoids by HPLC-DAD, volatile compounds by HS-SPME-GC–MS, and sensory profiles were studied. The decrease in tocopherols and secoiridoids was greater in "infusion" samples, while a significant increase in capsaicinoids was observed in "permanent infusion" samples. The main changes were observed for sensory and volatile profiles: "infusion" samples were defective already after 2 months with significant increase of defects-relating volatile compounds, while "co-milling" samples were defects-free and characterized by nice balance among hotness/heat and pepper fruity/taste during entire storage. "Co-milling" samples showed better shelf-life (18 months) than infusion ones, and even than EVOO control samples (12 months). • Chili peppers flavoured olive oil by co-milling and infusion were stored for18 months. • Co-milling and infused oils richer in phenols – vitamin E/capsaicinoids, respectively. • Major changes were on volatile and sensory defects of samples flavoured by infusion. • Oils by co-milling were free from defects with stable sensory profile up to 18 months. • Co-milling oils had better sensory and chemical shelf-life even than control sample. [ABSTRACT FROM AUTHOR]

Stress-induced monoubiquitination of p53 is a crucial event for the nuclear-cytoplasm-mitochondria trafficking and transcription-independent pro-apoptotic functions of p53. Although an intact ubiquitination pathway and a functional nuclear export sequence are required for p53 nuclear export, the role of specific residues within this region in regulating both processes remains largely unknown. Here we characterize the mechanisms accounting for the nuclear accumulation of a new point mutation (Lys-351 to Asn) in the nuclear export sequence of p53 identified in a cisplatin-resistant ovarian carcinoma cell line (A2780 CIS). We found that K351N substitution abrogates the monoubiquitination of p53 induced by both Mdm2 and MSL2 E3-ligases. As a consequence, cells expressing p53 K351N mutant showed defects in cisplatin-induced translocation of p53 to mitochondria, Bax oligomerization, and mitochondrial membrane depolarization. These data identify K351N as a critical mutation of p53 that contributes to the development and maintenance of resistance to cisplatin. [ABSTRACT FROM AUTHOR]

Summary: Che-1 is a RNA polymerase II binding protein involved in the regulation of gene transcription and, in response to DNA damage, promotes p53 transcription. In this study, we investigated whether Che-1 regulates mutant p53 expression. We found that Che-1 is required for sustaining mutant p53 expression in several cancer cell lines, and that Che-1 depletion by siRNA induces apoptosis both in vitro and in vivo. Notably, loss of Che-1 activates DNA damage checkpoint response and induces transactivation of p73. Therefore, these findings underline the important role that Che-1 has in survival of cells expressing mutant p53. [ABSTRACT FROM AUTHOR]