منابع مشابه
Proteotoxic stress targeted therapy (PSTT)
About a decade ago a multiple myeloma patient demonstrated a complete response to a proteasome inhibitor Bortezomib. This case generated a lot of hopes, and after successful clinical trials Bortezomib was approved by FDA and became the drug of choice for this disease. A high sensitivity of multiple myeloma to proteasome inhibition is probably related to extensive production immunoglobulins by t...
متن کاملProteotoxic stress targeted therapy (PSTT): induction of protein misfolding enhances the antitumor effect of the proteasome inhibitor bortezomib
Proteotoxic stress (PS) is generated in cells under a variety of conditions involving accumulation of misfolded proteins. To avoid the toxicity of unmitigated PS, cells activate the heat shock response (HSR). HSR involves upregulation of factors such as ubiquitin and the non-housekeeping chaperone Hsp70 which assist with metabolism of aberrant proteins. The PS-HSR axis is a potential anticancer...
متن کاملHow the Nucleus Copes with Proteotoxic Stress
The proper folding of proteins is continuously challenged by intrinsic and extrinsic stresses, and the accumulation of toxic misfolded proteins is associated with many human diseases. Eukaryotic cells have evolved a complex network of protein quality control pathways to protect the proteome, and these pathways are specialized for each subcellular compartment. While many details have been elucid...
متن کاملAneuploidy and proteotoxic stress in cancer
Although nearly ubiquitous in cancer, aneuploidy exerts detrimental effects on human cells. We recently demonstrated that aneuploid human cells exhibit impaired heat shock factor protein 1 (HSF1) and HSP90 function, suggesting a functional link between two recurring features of cancer cells: aneuploidy and proteotoxic stress. Further, our findings implicate HSF1 as a key factor in mitigating th...
متن کاملAneuploidy causes proteotoxic stress in yeast.
Gains or losses of entire chromosomes lead to aneuploidy, a condition tolerated poorly in all eukaryotes analyzed to date. How aneuploidy affects organismal and cellular physiology is poorly understood. We found that aneuploid budding yeast cells are under proteotoxic stress. Aneuploid strains are prone to aggregation of endogenous proteins as well as of ectopically expressed hard-to-fold prote...
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ژورنال
عنوان ژورنال: Oncotarget
سال: 2011
ISSN: 1949-2553
DOI: 10.18632/oncotarget.284