Structure and Function of the 26S Proteasome

Abstract

As the endpoint for the ubiquitin-proteasome system, the 26S proteasome is the principal proteolytic machine responsible for regulated protein degradation in eukaryotic cells. The proteasome's cellular functions range from general protein homeostasis and stress response to the control of vital processes such as cell division and signal transduction. To reliably process all the proteins presented to it in the complex cellular environment, the proteasome must combine high promiscuity with exceptional substrate selectivity. Recent structural and biochemical studies have shed new light on the many steps involved in proteasomal substrate processing, including recognition, deubiquitination, and ATP-driven translocation and unfolding. In addition, these studies revealed a complex conformational landscape that ensures proper substrate selection before the proteasome commits to processive degradation. These advances in our understanding of the proteasome's intricate machinery set the stage for future studies on how the proteasome functions as a major regulator of the eukaryotic proteome.

Retracted: Studies of proteasome inhibition and antitumor activity by novel amino acid‐polypyridine‐copper complexes

“…Single crystals of complexes 1 to 5 were used for X-ray diffraction analyses by mounting on the tip of a glass fiber in air. Crystal data were collected at 113 (2) or 293(2) or 386(2) K, using a Bruker SMART CCD 1000 diffractometer. Diffraction intensities for the complexes were collected by using the ω-scan technique.…”

“…The ubiquitin-proteasome system (UPS) plays an important role in multitude of cellular processes including: cell cycle progression, DNA damage and repair, endocytosis, apoptosis, angiogenesis, drug resistance and differentiation. [1][2][3][4] Proliferation and apoptosis pathways are tightly regulated in a cell by the UPS and alterations in the UPS may result in cellular transformation or other pathological conditions. Indeed, the proteasome is often found to be overactive in cancer cells.…”

Studies of proteasome inhibition and apoptosis induction in triple‐negative breast cancer cells by novel amino acid–polypyridine–copper complex

“…The samples were separated by SDS-PAGE, transferred to poly(vinylidene fluoride) membranes by electroblotting and probed with antibodies against p53 (1:2000, CST, 48818S), Bax [34] After washing, the membranes were incubated in IgG secondary antibody conjugated with alkaline phosphatase, followed by detection with ECL reagent (Millipore Bedford, MA, USA) and visualization on autoradiography film. Semi-quantification of blots (18) N(2)-Cu(1)-N(3) 82.0 (2) was performed using ImageJ software version 1.41o (National Institutes of Health, Bethesda, MD, USA).…”

“…The proteasome is the major intracellular proteolytic complex in eukaryotic cells, responsible for the degradation of ubiquitin‐tagged proteins and has a key role in protein turnover . As cancer cells are more sensitive to proteasome inhibition than their normal counterparts, and inhibition leads to accumulation of substrate proteins and ultimately to cell death, proteasome inhibitors have been considered for some time as potential novel anticancer therapy .…”

“…The proteasome is the major intracellular proteolytic complex in eukaryotic cells, responsible for the degradation of ubiquitin-tagged proteins and has a key role in protein turnover. [1][2][3][4] As cancer cells are more sensitive to proteasome inhibition than their normal counterparts, and inhibition leads to accumulation of substrate proteins and ultimately to cell death, proteasome inhibitors have been considered for some time as potential novel anticancer therapy. [5][6][7][8][9] This is important as proteasome inhibitors have demonstrated clinical efficacy in the treatment of malignancies by activation of apoptosis and paraptosis as well as by prevention of angiogenesis and metastasis.…”