Dawid Walerych

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Breast cancer is the most frequent invasive tumor diagnosed in women, causing over 400 000 deaths yearly worldwide. Like other tumors, it is a disease with a complex, heterogeneous genetic and biochemical background. No single genomic or metabolic condition can be regarded as decisive for its formation and progression. However, a few key players can be(More)
Humans contain many HSP (heat-shock protein) 70/HSPA- and HSP40/DNAJ-encoding genes and most of the corresponding proteins are localized in the cytosol. To test for possible functional differences and/or substrate specificity, we assessed the effect of overexpression of each of these HSPs on refolding of heat-denatured luciferase and on the suppression of(More)
Immortalized human fibroblasts were used to investigate the putative interactions of the Hsp90 molecular chaperone with the wild-type p53 tumor suppressor protein. We show that geldanamycin or radicicol, specific inhibitors of Hsp90, diminish specific wild-type p53 binding to the p21 promoter sequence. Consequently, these inhibitors decrease p21 mRNA(More)
The activity and structural integrity of the tumor suppressor protein p53 is of crucial importance for the prevention of cancer. p53 is a conformational flexible and labile protein, in which structured and unstructured regions function in a synergistic manner. The molecular chaperone Hsp90 is known to bind to mutant and wild type p53 in vivo. Using highly(More)
p53 as an unstable protein in vitro likely requires stabilizing factors to act as a tumor suppressor in vivo. Here, we show that in human cells transfected with wild-type (WT) p53, Hsp90 and Hsp70 molecular chaperones maintain the p53 native conformation under heat-shock conditions (42 degrees C) as well as assist p53 refolding at 37 degrees C, during the(More)
Cisplatin and its derivatives are commonly used anti-cancer drugs. However, cisplatin has clinical limitations including serious side effects and frequent emergence of intrinsic or acquired resistance. Thus, the novel platinum(IV) complex LA-12 represents a promising treatment modality, which shows increased intracellular penetration resulting in improved(More)
Hsp90 is a ubiquitous, ATP-dependent chaperone, essential for eukaryotes. It possesses a broad spectrum of substrates, among which is the p53 transcription factor, encoded by a tumor-suppressor gene. Here, we elucidate the role of the adenine nucleotide in the Hsp90 chaperone cycle, by taking advantage of a unique in vitro assay measuring Hsp90-dependent(More)
The TP53 tumor suppressor is the most frequently mutated gene in human cancers. In recent years, a blooming of research efforts based on both cell lines and mouse models have highlighted how deeply mutant p53 proteins affect fundamental cellular pathways with cancer-promoting outcomes. Neomorphic mutant p53 activities spread over multiple levels, impinging(More)
Downregulation of microRNAs (miRNAs) is commonly observed in cancers and promotes tumorigenesis suggesting that miRNAs may function as tumor suppressors. However, the mechanism through which miRNAs are regulated in cancer, and the connection between oncogenes and miRNA biogenesis remain poorly understood. The TP53 tumor-suppressor gene is mutated in half of(More)
Encoded by the mutated variants of the TP53 tumor suppressor gene, mutant p53 proteins are getting an increased experimental support as active oncoproteins promoting tumor growth and metastasis. p53 missense mutant proteins are losing their wild-type tumor suppressor activity and acquire oncogenic potential, possessing diverse transforming abilities in cell(More)