Estrogen receptor mediates a distinct mitochondrial unfolded protein response

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Estrogen receptor mediates a distinct mitochondrial unfolded protein response.

Unfolded protein responses (UPRs) of the endoplasmic reticulum and mitochondrial matrix have been described. Here, we show that the accumulation of proteins in the inter-membrane space (IMS) of mitochondria in the breast cancer cell line MCF-7 activates a distinct UPR. Upon IMS stress, overproduction of reactive oxygen species (ROS) and phosphorylation of AKT triggers estrogen receptor (ER) act...

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Estrogen receptor α inhibitor activates the unfolded protein response, blocks protein synthesis, and induces tumor regression.

Recurrent estrogen receptor α (ERα)-positive breast and ovarian cancers are often therapy resistant. Using screening and functional validation, we identified BHPI, a potent noncompetitive small molecule ERα biomodulator that selectively blocks proliferation of drug-resistant ERα-positive breast and ovarian cancer cells. In a mouse xenograft model of breast cancer, BHPI induced rapid and substan...

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Intracellular Eukaryotic Parasites Have a Distinct Unfolded Protein Response

Insult to the endoplasmic reticulum (ER) activates the Unfolded Protein Response (UPR), a set of signaling pathways that protect the cell from the potential damage caused by improperly folded proteins. Accumulation of misfolded proteins in the ER lumen initiates a series of signal transduction events via activation of three transmembrane ER proteins: Ire1, Atf6 and PERK. Activation of these pro...

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mtDNA, Metastasis, and the Mitochondrial Unfolded Protein Response (UPRmt)

While several studies have confirmed a link between mitochondrial DNA (mtDNA) mutations and cancer cell metastasis, much debate remains regarding the nature of the alternations in mtDNA leading to this effect. Meanwhile, the mitochondrial unfolded protein response (UPRmt) has gained much attention in recent years, with most studies of this pathway focusing on its role in aging. However, the UPR...

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The unfolded protein response

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ژورنال

عنوان ژورنال: Journal of Cell Science

سال: 2011

ISSN: 1477-9137,0021-9533

DOI: 10.1242/jcs.078220