ABSTRACT
As a tumor suppressor, p53 preserves genomic integrity in eukaryotes. However, limited evidence is availablefor the p53 shuttling between the cytoplasm and nucleus. Previous studies have shown that b-actin polymerization negatively regulates p53 nuclear import through its interaction with p53. In this study, we found thatDNA damage induces both b-actin and p53 accumulation in the nucleus. b-actin knockdown impaired thenuclear transport of p53. Additionally, b-actin could interact with p53 which was enhanced in response togenotoxic stress. Furthermore, N terminal deletion mutants of p53 shows reduced levels of association with bactin. We further identified Ser15, Thr18 and Ser20 of p53 are critical to the b-actin: p53 interaction, whichupon mutation into alanine abrogates the binding. Taken together, this study reveals that b-actin regulates thenuclear import of p53 through protein–protein interaction.
ABSTRACT
Aims: The acquired cholesteatoma, even with all the knowledge accumulated since its first description, still remains a public health problem, far from being solved. A deeper understanding of its pathogenesis is extremely important since it is a destructive lesion that might cause potentially serious complications. We had the objective, in this study, to identify acquired cholesteatoma biomarkers using proteomics platform. Study Design: descriptive cross-sectional study. Methodology: Samples were collected from cholesteatoma and also from the retroauricular skin of twelve patients undergoing surgery for cholesteatoma removal. The samples were studied by proteomic analysis, using the Mascot algorithm and the NCBI and Swiss Prot proteins database. Results: Of the 393 spots identified in the analysis of protein extracts of acquired cholesteatoma, only 10 were within acceptable statistical parameters by Mascot algorithm. The proteins detected in acquired cholesteatoma were fibrinogen beta chain, extracellular matrix protein 2, actin cytoplasmic 1, heparan sulfate glucosamine 3-O-sulfotransferase 3A1, tumor necrosis factor alpha 8 induced protein-like 1, stanniocalcin-2, eosinophil lysophospholipase and OFUT1. Conclusion: Proteins involved in cell migration, regulation of apoptosis, signaling pathways, cellular proliferation, wound healing and inflammatory processes were identified. We were able to draw a proteomic profile of acquired cholesteatoma.