Most forms of neuronal plasticity are associated with induction of the transcription factor Zif268 (Egr1/Krox24/NGF-IA). In a genome-wide scan, we obtained evidence for potential modulation of proteasome subunit and regulatory genes by Zif268 in neurons, a finding of significance considering emerging evidence that the proteasome modulates synaptic function. Bioinformatic analysis indicated that...

A long-lasting renal ischemia, followed by the left renal artery clipping (two-kidney, one clip Goldblatt model in rats) led to a marked decrease in proteasome chymotrypsin-like activity in the ischemic kidney. This activity was, however, significantly raised upon the stimulation with an artificial 20S proteasome activator SDS (0.025%). No changes were observed in either the levels of the const...

ubiquitin, and then degraded by a proteasome in an ATP dependent manner1^ The catalytic core of the proteasome is the 20S proteasome. New20S proteasome inhibitors would contribute to further understanding of the system2~4\ In the course of our screening program, wehave isolated several classes of 20S proteasome inhibitors including (i) the novel cyclic peptides, TMC-95s, and (ii) the new member...

T-cell acute lymphoblastic leukemia is an aggressive hematologic malignancy which is usuallyassociated with unfavorable prognosis particularly in patients with refractory/relapsed disease.Therefore, development of novel therapeutic strategies is highly required for improving theoutcome of these patients. Although there are several studies evaluating the efficacy of proteasome<...

Proteasomes are essential for protein homeostasis in eukaryotes. To preserve cellular function, transcription of proteasome subunit genes is induced in response to proteasome dysfunction caused by pathogen attacks or proteasome inhibitor drugs. In Caenorhabditis elegans, this response requires SKN-1, a transcription factor related to mammalian Nrf1/2. Here, we use comprehensive genetic analyses...

In Saccharomyces cerevisiae, chemical or genetic inhibition of proteasome activity induces new proteasome synthesis promoted by the transcription factor RPN4. This ensures that proteasome activity is matched to demand. This transcriptional feedback loop is conserved in mammals, but its molecular basis is not understood. Here, we report that nuclear factor erythroid-derived 2-related factor 1 (N...

Assembly of the eukaryotic 20S proteasome is an ordered process involving several proteins operating as proteasome assembly factors including PAC1-PAC2 but archaeal 20S proteasome subunits can spontaneously assemble into an active cylindrical architecture. Recent bioinformatic analysis identified archaeal PAC1-PAC2 homologs PbaA and PbaB. However, it remains unclear whether such assembly factor...

The three-dimensional fold of Plasmodium falciparum (Pf) 20S proteasome is similar to yeast Saccharomyces cerevisiae 20S proteasome. The twenty eight subunits complex corresponding to two copies of seven distinct α and seven distinct β subunits shares >35% sequence identity with equivalent subunits of the yeast 20S proteasome. Bortezomib (Velcade®) - a known inhibitor of the three catalytic sub...

Several lines of evidence suggest that proteasomes are involved in multiple aspects of myocardial physiology and pathology, including myocardial ischemia-reperfusion injury. It is well established that the 26S proteasome is an ATP-dependent enzyme and that ischemic heart disease is associated with changes in the ATP content of the cardiomyocyte. A functional link between the 26S proteasome, myo...