This study identifies the main changes in protein expression in human breast tumors compared to normal breast tissue. Malignant tumors (32) and normal breast tissue samples (23), from formaldehyde-fixed, paraffin-embedded specimens are subjected to discovery proteomics using liquid chromatography/tandem mass spectrometry, with spectral counts for quantitation. The dataset contains 1406 proteins. Differential expression is measured using a method that takes advantage of estimates of the percentage of tumor on a slide. This analysis shows that the major classes of proteins over-expressed by tumors are RNA-binding, heat shock and DNA repair proteins. RNA-binding proteins, including heterogeneous nuclear ribonucleoproteins (HNRNPs), SR splice factors (SRSF) and elongation factors form the largest group. Comparison with results from another study demonstrates that the RNA-binding proteins are associated specifically with malignant transformation, rather than with cell proliferation. HNRNP and SRSF proteins help define splice sites in normal cells. Their over-expression may dysregulate splicing, which in turn has the potential to promote malignant transformation.
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http://dx.doi.org/10.1002/pmic.202000044 | DOI Listing |
Biol Chem
January 2025
Cell Biology Center, Institute of Integrated Research, Institute of Science Tokyo (Formerly Tokyo Institute of Technology), S2-19, Nagatsuta 4259, Midori-ku, Yokohama, 226-8501, Japan.
The heat stress response is an essential defense mechanism in all organisms. Heat shock proteins (Hsps) are produced in response to thermal stress, with their expression levels regulated by heat shock transcription factors. In the key transcription factor σ positively regulates Hsp expression.
View Article and Find Full Text PDFFASEB J
January 2025
Department of Biochemistry and Molecular Biology, Institute of Marine and Environmental Technology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Molecular chaperones play critical roles in post-translational maintenance in protein homeostasis. Previous studies have shown that loss of Smyd1b function results in defective myofibril organization and dramatic upregulation of heat shock protein gene (hsp) expression in muscle cells of zebrafish embryos. To investigate the molecular mechanisms and functional importance of this stress response, we characterized changes of gene expression in smyd1b knockdown and knockout embryos using RNA-seq.
View Article and Find Full Text PDFiScience
November 2024
Department of Drug Discovery and Development, Harrison College of Pharmacy, Auburn University, 720 S. Donahue Dr., Auburn, AL, USA.
Bruton's tyrosine kinase (BTK) inhibitor, ibrutinib, has been shown to synergize with proteasome inhibitors (PIs) in reducing the viability of cells derived from B cell malignancies, but the mechanism is not known. We report here that an off-target effect of ibrutinib causes synergy because not all BTK inhibitors exhibited the synergistic effect, and those that synergized did so even in cells that do not express BTK. The allosteric BTK inhibitor CGI-1746 showed the strongest synergy.
View Article and Find Full Text PDFComp Biochem Physiol A Mol Integr Physiol
January 2025
Beijing Normal University, Beijing 100875, China; State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Science, Beijing 100012, China.
The prevalence of heatwave and hypoxia events and their devastating impacts on aquatic ecosystems and fishery resources reinforces the priority of research to address the resilience and adaption mechanisms to these two stressors in important fish species. However, our understanding of the development of cross-tolerance of these two stressors in fish still limited. Here, we investigated the impacts of prior heatwave exposure on hypoxia tolerance and the underlying mechanisms in silver carp (Hypophthalmichthys molitrix), a species of considerable ecological and commercial importance.
View Article and Find Full Text PDFDrug Discov Today
January 2025
Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, School of Pharmaceutical Sciences, Hunan Normal University, Changsha 410013, Hunan, China. Electronic address:
The heat shock protein (HSP) 110 family has a key role as a unique class of molecular chaperones maintaining cellular proteostasis in eukaryotes. Abnormal activation of Hsp110 has been implicated in several diseases. Given its important role in pathogenesis, Hsp110 has become a novel drug target for disease diagnosis and targeted therapy.
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