Many drugs currently used in chemotherapy work by hindering the process of ribosome biogenesis. In tumors with functional p53, the inhibition of ribosome biogenesis may contribute to the efficacy of this treatment by inducing p53 stabilization. As the level of stabilized p53 is critical for the induction of cytotoxic effects, it seems useful to highlight those cancer cell characteristics that can predict the degree of p53 stabilization following the treatment with inhibitors of ribosome biogenesis. In the present study we exposed a series of p53 wild-type human cancer cell lines to drugs such as actinomycin D (ActD), doxorubicin, 5-fluorouracil and CX-5461, which hinder ribosomal RNA (rRNA) synthesis. We found that the amount of stabilized p53 was directly related to the level of ribosome biogenesis in cells before the drug treatment. This was due to different levels of inactivation of the ribosomal proteins-MDM2 pathway of p53 digestion. Inhibition of rRNA synthesis always caused cell cycle arrest, independent of the ribosome biogenesis rate of the cells, whereas apoptosis occurred only in cells with a high rDNA transcription rate. The level of p53 stabilization induced by drugs acting in different ways from the inhibition of ribosome biogenesis, such as hydroxyurea (HU) and nutlin-3, was independent of the level of ribosome biogenesis in cells and always lower than that occurring after the inhibition of rRNA synthesis. Interestingly, in cells with a low ribosome biogenesis rate, the combined treatment with ActD and HU exerted an additive effect on p53 stabilization. These results indicated that (i) drugs inhibiting ribosome biogenesis may be highly effective in p53 wild-type cancers with a high ribosome biogenesis rate, as they induce apoptotic cell death, and (ii) the combination of drugs capable of stabilizing p53 through different mechanisms may be useful for treating cancers with a low ribosome biogenesis rate.
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http://dx.doi.org/10.1038/onc.2015.147 | DOI Listing |
Zhongguo Dang Dai Er Ke Za Zhi
January 2025
Department of Pediatrics, Third People's Hospital of Longgang District of Shenzhen, Shenzhen, Guangdong 518020, China.
Objectives: To explore the role of berberine (BBR) in ameliorating coronary endothelial cell injury in Kawasaki disease (KD) by regulating the complement and coagulation cascade.
Methods: Human coronary artery endothelial cells (HCAEC) were divided into a healthy control group, a KD group, and a BBR treatment group (=3 for each group). The healthy control group and KD group were supplemented with 15% serum from healthy children and KD patients, respectively, while the BBR treatment group received 15% serum from KD patients followed by the addition of 20 mmol/L BBR.
BMC Genomics
January 2025
Key Laboratory of Ecological Protection and Restoration of Typical Plateau Wetlands, Bijie, Guizhou Province, 551700, China.
Background: Temperature is a key determinant of ectotherms distribution and growth. During the Eriocheir sinensis breeding process, it was observed that crabs in high latitudes and altitude areas with low temperatures undergo diapause, they would overwinter and continue to grow into three-year-old individuals, whose final body size is significantly larger than the normal two-year-old crabs. The hepatopancreas is responsible for maintaining the nutritional balance and energy required for the crab survival.
View Article and Find Full Text PDFJ Bacteriol
January 2025
Department of Microbiology, Howard Taylor Ricketts Laboratory, The University of Chicago, Chicago, Illinois, USA.
Protein secretion is an essential cell process in bacteria, required for cell envelope biogenesis, export of virulence factors, and acquisition of nutrients, among other important functions. In the Sec secretion pathway, signal peptide-bearing precursors are recognized by the SecA ATPase and pushed across the membrane through a translocon channel made of the proteins SecY, SecE, and SecG. The Sec pathway has been extensively studied in the model organism , but the Sec pathways of other bacteria such as the human pathogen differ in important ways from this model.
View Article and Find Full Text PDFMol Oncol
January 2025
Institut Curie, Inserm U932 - Immunity and Cancer, Paris, France.
Transposable elements provide material for novel gene formation. In particular, DNA transposons have contributed several essential genes involved in various physiological or pathological conditions. Here, we discuss recent findings by Tu et al.
View Article and Find Full Text PDFNat Commun
January 2025
Molecular Genetics of Eukaryotes, University of Kaiserslautern, Kaiserslautern, Germany.
Molecular chaperones are essential throughout a protein's life and act already during protein synthesis. Bacteria and chloroplasts of plant cells share the ribosome-associated chaperone trigger factor (Tig1 in plastids), facilitating maturation of emerging nascent polypeptides. While typical trigger factor chaperones employ three domains for their task, the here described truncated form, Tig2, contains just the ribosome binding domain.
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