Based on the existing structure activity relationship for proteasome inhibitors, a number of substituted aryl-2-nitrovinyl derivatives have been synthesized as Michael acceptor and their cytotoxicity and proteasome inhibitory effects were evaluated on two cancer cell lines. Compound 2d exhibited IC50 values of 0.71 and 17.79 μM comparable to bortezomib against MCF-7 and PC-3, respectively. The ...

Based on the existing structure activity relationship for proteasome inhibitors, a number of substituted aryl-2-nitrovinyl derivatives have been synthesized as Michael acceptor and their cytotoxicity and proteasome inhibitory effects were evaluated on two cancer cell lines. Compound 2d exhibited IC50 values of 0.71 and 17.79 μM comparable to bortezomib against MCF-7 and PC-3, respectively. The ...

Background: The ubiquitin-proteasome system (UPS) plays a crucial role in regulating the levels and functions of a large number of proteins in the cell, which are important for cancer cell growth and survival. The proteasome is highly activated in B-cell precursor acute lymphoblastic leukemia (BCP-ALL), which is the most common malignancy in children. The attempt to inhibit proteasome as a ther...

Background/Aim: Androgen receptor (AR) degradation is the primary regulator of androgen activity. This study was designed to investigate influence proteasome on AR protein stability after enzalutamide (Enz) treatment. Materials and Methods: Cell counting treatment utilized assess effect Enz cell proliferation. Changes in mRNA levels were evaluated using reverse transcription-polymerase chain re...

Objective(s): In this study, potential protective effects of Bortezomib (Bort), as a proteasome inhibitor, were investigated on the uterus of ovariectomized rats by histological, morphometric and immunohistochemical methods.Materials and Methods: In this study, 18 Sprague dawley strain female rats (12 weeks old, 250-300 g body weight) were used. Animals in the control group (Cont, n=6) were not...

Protein degradation by the 26S proteasome is a fundamental process involved in a broad range of cellular activities, yet how proteasome activity is regulated remains poorly understood. We report here that ubiquitin-like domain-containing C-terminal domain phosphatase 1 (UBLCP1) is a 26S proteasome phosphatase that regulates nuclear proteasome activity. UBLCP1 directly interacts with the proteas...

Ubiquitin-dependent protein degradation is essential for cells to survive many environmental stresses. Thus, it may be necessary to buffer ubiquitin and proteasome pools against fluctuation. Proteasome levels are tightly regulated, and proteasome deficiency stimulates a stress response. Here we report a novel pathway of cellular response to ubiquitin depletion. Unlike proteasome stress, ubiquit...

Proteasome degrades proteins in eukaryotic cells. As such, the proteasome is crucial in cell cycle and function. This study proved that microcystin-LR (MC-LR), which is a toxic by-product of algal bloom, can target cellular proteasome and selectively inhibit proteasome trypsin-like (TL) activity. MC-LR at 1 nM can inhibit up to 54% of the purified 20S proteasome TL activity and 43% of the prote...

20S proteasome is the enzymatic core engine involved in processes of cellular protein regulation, thus becoming a promising target inter alia therapy many diseases. In this work, ...