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 levels, which lead to a reduction in cellula...

BACKGROUND In the last two decades, pioneering research on anti-tumour activity of saffron has shed light on the role of crocetin, picrocrocin and safranal, as broad spectrum anti-neoplastic agents. However, the exact mechanisms have yet to be elucidated. Identification and characterization of the targets of bioactive constituents will play an imperative role in demystifying the complex anti-ne...

In the present study we investigated the substrate-binding characteristics of three members of the 90 kDa heat shock protein (HSP90) family, namely the alpha isoform of human HSP90 (HSP90alpha), human GRP94 (94 kDa glucose-regulated protein, a form of HSP90 from endoplasmic reticulum), and HtpG (the Escherichia coli homologue of HSP90) and the domain responsible for these characteristics. The r...

The 90-kDa heat-shock protein (Hsp90) operates in the context of a multichaperone complex to promote maturation of nuclear and cytoplasmic clients. We have discovered that Hsp90 and the cochaperone Sba1/p23 accumulate in the nucleus of quiescent Saccharomyces cerevisiae cells. Hsp90 nuclear accumulation was unaffected in sba1Delta cells, demonstrating that Hsp82 translocates independently of Sb...

Hypoxia-inducible factor 1 alpha (HIF-1 alpha) and the intracellular dioxin receptor mediate hypoxia and dioxin signalling, respectively. Both proteins are conditionally regulated basic helix-loop-helix (bHLH) transcription factors that, in addition to the bHLH motif, share a Per-Arnt-Sim (PAS) region of homology and form heterodimeric complexes with the common bHLH/PAS partner factor Arnt. Her...

PURPOSE These studies were designed to determine whether ritonavir inhibits breast cancer in vitro and in vivo and, if so, how. EXPERIMENTAL DESIGN Ritonavir effects on breast cancer cell growth were studied in the estrogen receptor (ER)-positive lines MCF7 and T47D and in the ER-negative lines MDA-MB-436 and MDA-MB-231. Effects of ritonavir on Rb-regulated and Akt-mediated cell proliferation...

Toll-like receptors (TLRs) play a crucial role in innate immunity by recognizing microbial pathogens. Triad3A is an E3 ubiquitin-protein ligase that interacts with the Toll/interleukin-1 receptor domain of TLRs and promotes their proteolytic degradation. In the present study, we further investigated its activity on signaling molecules downstream of TLRs and tumor necrosis factor (TNF) receptor ...

Members of the Hsp90 family of molecular chaperones play important roles in allowing some intracellular signaling molecules and transcription factors to reach and maintain functionally active conformations. In the present study, we have utilized the specific Hsp90-binding agent, geldanamycin, to examine the requirement for Hsp90 during zebrafish development. We show that geldanamycin interacts ...

Aromatase inhibitors are important drugs to treat estrogen receptor alpha (ERalpha)-positive postmenopausal breast cancer patients. However, development of resistance to aromatase inhibitors has been observed. We examined whether the heat shock protein 90 (HSP90) inhibitor 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG) can inhibit the growth of aromatase inhibitor-resistant bre...

In an effort to provide a more powerful system to study the Ah receptor (AHR) signaling pathway, we expressed the AHR, its dimerization partner ARNT, and a beta-galactosidase (lacZ) reporter gene, driven by two dioxin-responsive enhancers, in the yeast Saccharomyces cerevisiae. In this system, the agonists beta-naphthoflavone and alpha-naphthoflavone induced transcription of the lacZ gene, with...