scholarly journals The next generation proteasome inhibitors carfilzomib and oprozomib activate prosurvival autophagy via induction of the unfolded protein response and ATF4

Autophagy ◽  
2012 ◽  
Vol 8 (12) ◽  
pp. 1873-1874 ◽  
Author(s):  
Yan Zang ◽  
Sufi M. Thomas ◽  
Elena T. Chan ◽  
Christopher J. Kirk ◽  
Maria L. Freilino ◽  
...  
Keyword(s):  
Unfolded Protein Response ◽  
Proteasome Inhibitors ◽  
Next Generation ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

scholarly journals BET Inhibitors Synergize with Carfilzomib to Induce Cell Death in Cancer Cells via Impairing Nrf1 Transcriptional Activity and Exacerbating the Unfolded Protein Response

Biomolecules ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 501 ◽  
Author(s):  
Janakiram R. Vangala ◽  
Ajay Potluri ◽  
Senthil K. Radhakrishnan
Keyword(s):  
Unfolded Protein Response ◽  
Solid Tumors ◽  
Cell Lines ◽  
Proteasome Inhibitors ◽  
Proteasome Inhibition ◽  
Therapeutic Modality ◽  
Unfolded Protein ◽  
Bet Inhibitors ◽  
The Unfolded Protein Response ◽  
Protein Response

Currently, proteasome inhibitors bortezomib, carfilzomib, and ixazomib are successfully used in clinics to treat multiple myeloma. However, these agents show limited efficacy against solid tumors. Identification of drugs that can potentiate the action of proteasome inhibitors could help expand the use of this therapeutic modality to solid tumors. Here, we found that bromodomain extra-terminal (BET) family protein inhibitors such as JQ1, I-BET762, and I-BET151 synergize with carfilzomib in multiple solid tumor cell lines. Mechanistically, BET inhibitors attenuated the ability of the transcription factor Nrf1 to induce proteasome genes in response to proteasome inhibition, thus, impeding the bounce-back response of proteasome activity, a critical pathway by which cells cope with proteotoxic stress. Moreover, we found that treatment with BET inhibitors or depletion of Nrf1 exacerbated the unfolded protein response (UPR), signaling that was initiated by proteasome inhibition. Taken together, our work provides a mechanistic explanation behind the synergy between proteasome and BET inhibitors in cancer cell lines and could prompt future preclinical and clinical studies aimed at further investigating this combination.

scholarly journals Next-generation proteasome inhibitor oprozomib synergizes with modulators of the unfolded protein response to suppress hepatocellular carcinoma

Oncotarget ◽  
2016 ◽  
Vol 7 (23) ◽  
pp. 34988-35000 ◽  
Author(s):  
Yves-Paul Vandewynckel ◽  
Céline Coucke ◽  
Debby Laukens ◽  
Lindsey Devisscher ◽  
Annelies Paridaens ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Unfolded Protein Response ◽  
Proteasome Inhibitor ◽  
Next Generation ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

Oestrogen-driven changes in the bovine uterus are associated with activation of the unfolded protein response

2014 ◽  
Author(s):  
Mohammed A Alfattah ◽  
Paul Anthony McGettigan ◽  
John Arthur Browne ◽  
Khalid M Alkhodair ◽  
Katarzyna Pluta ◽  
...  
Keyword(s):  
Unfolded Protein Response ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response
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