Proteasome inhibition has been recognized as a novel treatment modality in hematologic malignancies. Initially, the reversible proteasome inhibitor bortezomib demonstrated efficacy in multiple myeloma (MM), which supported its approval for relapsed and refractory MM in 2003. Later on, carfilzomib, a next-generation irreversible proteasome inhibitor was approved by the US FDA in July 2012 for re...

Proteasome inhibitors (e.g., bortezomib, MG132) are known to enhance adeno-associated virus (AAV) transduction; however, whether this results from pleotropic proteasome inhibition or off-target serine and/or cysteine protease inhibition remains unresolved. Here, we examined recombinant AAV (rAAV) effects of a new proteasome inhibitor, carfilzomib, which specifically inhibits chymotrypsin-like p...

Proteasome inhibitors are currently used as chemotherapeutic drugs because of their ability to block NF-kappaB, a transcription factor constitutively activated in many different types of human cancer. In the present study, we demonstrate that proteasome inhibitors induce cell death in endometrial carcinoma cell lines and primary explants but, instead of blocking NF-kappaB, they increase its tra...

Abstract "Superhenhanced" transcription of specific oncogenes by aberrant looping upstream enhancer elements to marked transcriptional regulatory regions is a mechanism oncogene overexpression. Therefore, compounds that target key positive regulators RNA polymerase II (RNAPII) activity, such as CDK7 and CDK9, can relatively selectively reduce expression superenhanced are in clinical trials. We ...

The present study demonstrates that even brief inhibition of degradation by the 26S proteasome inhibits global protein synthesis, mediated through increased phosphorylation of eIF2alpha (eukaryotic translational initiation factor 2alpha) by the HRI (haem-regulated inhibitor) kinase. Exposure of COS-7 cells to the proteasome inhibitor MG-132 (the proteasome inhibitor carbobenzoxy-L-leucyl-L-leuc...

Cutaneous T-cell lymphoma (CTCL) is a non-Hodgkin that presents with skin manifestations and often incurable at advanced stages blood involvement. Genomic profiling of malignant cells from CTCL patients has revealed diverse range genetic mutations underlying the disease, including single nucleotide gene copy number alterations involving JAK/STAT NF-κB signaling pathways. Synergistic drug combin...

The proteasome, the multiprotein complex that is responsible for a large portion of protein degradation in the cell, has captured the interest of scientists from diverse areas, including evolutionary biology, the biochemistry of proteolysis, and drug discovery. Indeed, the recent approval of the proteasome inhibitor bortezomib for the treatment of multiple myeloma underscores the value of under...