Proteasomes

BTG/Tob family proteins, which are characterized by similarities in their N-terminal BTG/Tob homology domains, control cell growth negatively. Among the BTG/ Tob family members, BTG2/TIS21/PC3 proteins have been reported to have short lives and to be degraded by the proteasome. However, the mechanisms regulating the stabilities of other BTG/Tob family proteins have not yet been clarified.

9p research12 01-06-2013 30 4   Download

The regulator of ubiquitous kinase (Ruk) protein, also known as CIN85 or SETA, is an adaptor-type protein belonging to the CD2AP/CMS family. It was found in complexes with many signaling proteins, including phos1 phoinositol (PtdIns) 3-kinase (EC 2.7.1.137), Cbl, GRB2, p130Cas and Crk. Functional analysis of these interactions, implicated Ruk in the regulation of apoptosis, receptor endocytosis and cytoskeletal rearrangements.

7p research12 01-06-2013 27 4   Download

Antizyme is a polyamine-induced cellular protein that binds to ornithine decarboxylase (ODC), and targets it to rapid ubiquitin-independent degradation by the 26S proteasome. However, the metabolic fate of antizyme is not clear. We have tested the stability of antizyme in mammalian cells. In contrast with previous studies demonstrating stability in vitro in a reticulocyte lysate-based degradation system, in cells antizyme is rapidly degraded and this degradation is inhibited by specific proteasome inhibitors. ...

7p research12 01-06-2013 40 3   Download

We previously demonstrated inmast cell lines RBL2H3 and FMA3 that tryptophan hydroxylase (TPH) undergoes very fast turnover driven by 26S-proteasomes [Kojima, M., Oguro, K., Sawabe, K., Iida, Y., Ikeda, R., Yamashita, A., Nakanishi, N. & Hasegawa, H. (2000)J.Biochem (Tokyo) 2000,127, 121–127]. In the present study, we have examined an involvement of TPH phosphorylation in the rapid turn-over, using non-neural TPH.

9p research12 29-04-2013 38 3   Download

The 26S proteasome, a protein complex consisting of a 20S proteasome and a pair of 19S regulatory particles (RP), is involved in ATP-dependent proteolysis in eukaryotes. In yeast, theRP contains six different ATPase subunits and, at least, 11 non-ATPase subunits. In this study, we identi®ed the rice homologs of yeast RP subunit genes from the rice expressed sequence tag (EST) library.

10p research12 29-04-2013 39 3   Download

Anti-Ras intracellular antibodies inhibit cell proliferation in vivo by sequestering the antigen and diverting it from its physiological location [Lener,M.,Horn, I.R.,Cardinale,A., Messina, S., Nielsen, U.B., Rybak, S.M., Hoogenboom, H.R., Cattaneo, A., Biocca, S. (2000)Eur. J. Biochem.267, 1196–1205]. Here we demonstrate that strongly aggregating single-chain antibody fragments (scFv), binding to Ras, induce apoptosis, and this effect is strictly related to the antibody-mediated aggregation of p21Ras.

9p tumor12 20-04-2013 40 3   Download

Metabolically unstable proteins are involved in a multitude of regulatory networks, including those that control cell signaling, the cell cycle and in many responses to physiological stress. In the present study, we have deter-mined the stability and characterized the degradation process of some members of the Gq class of heterotrimeric G proteins. Pulse-chase experi-ments in HEK293 cells indicated a rapid turnover of endogenously expressed Gaq and overexpressed Gaq and Ga16 subunits.

13p fptmusic 12-04-2013 37 2   Download

The COP9 signalosome (CSN) occurs in all eukaryotic cells. It is a regula-tory particle of the ubiquitin (Ub)⁄26S proteasome system. The eight sub-units of the CSN possess sequence homologies with the polypeptides of the 26S proteasome lid complex and just like the lid, the CSN consists of six subunits with PCI (proteasome, COP9 signalosome, initiation factor 3) domains and two components with MPN (Mpr-Pad1-N-terminal) domains.

9p fptmusic 11-04-2013 22 1   Download

Parkinson’s disease is characterized by the loss of dopaminergic neurons in the nigrostriatal pathway accompanied by the presence of intracellular cytoplasmic inclusions, termed Lewy bodies. Fibrillized a-synuclein forms the major component of Lewy bodies. We reported a specific interaction between rata-synuclein and tat binding protein 1, a subunit of PA700, the regulatory complex of the 26S proteasome.

11p fptmusic 11-04-2013 37 1   Download

Purified, nonubiquitinated growth-associated protein of 43 kDa (GAP-43) was attacked by purified reticulocyte 20S proteasomebutnotby the26Sproteasome.Cleavageyielded 12 N-terminally labelled GAP-43 fragments that could be resolved by SDS/PAGE. Inhibitor experiments suggested that proteasomeb1 activity yielded the resolved bands and that proteasome b5 activity generated nonresolvable frag-ments. Processive degradation, yielding only nonresolvable fragments, therefore did not occur.

14p dell39 03-04-2013 33 3   Download

NEDD8 is a ubiquitin-like protein that controls vital bio-logical events through its conjugation to target proteins. Previously, we identifieda negative regulator oftheNEDD8 conjugation system, NEDD8 ultimate buster-1 (NUB1), that recruits NEDD8 and its conjugates to the proteasome for degradation. Recently, we performed yeast two-hybrid screening with NUB1 as bait and isolated a ubiquitin pre-cursor UbC1 that is composed ofnine tandem repeats of a ubiquitin unit through a-peptide bonds.

11p dell39 03-04-2013 31 5   Download

The eukaryotic translation initiation factor (eIF) 4E, is regulated by modulating both its phosphorylation and its availability to interact with the scaffold protein, eIF4G, to form the mature eIF4F complex. Here we show that treat-ment of C2C12 myoblasts with the proteasomal inhibitor, MG132 (N-carbobenzoxyl-Leu-Leu-leucinal), resulted in an early decrease inprotein synthesis rates followed by a partial recovery, reflecting the reprogramming of translation.

16p dell39 03-04-2013 45 4   Download

The Rpn10 subunit of the 26S proteasome can bind to polyubiqui-tinoylated and⁄or ubiquitin-like proteins via ubiquitin-interacting motifs (UIMs). Vertebrate Rpn10 consists of five distinct spliced isoforms, but the specific functions of these variants remain largely unknown.

14p dell39 27-03-2013 46 4   Download

The aim of our studies is to get access to as much as possible of the protein species present in the proteome under analysis. Already at the low complexity level of proteasomes it becomes clear that proteins are massively modified. There are about 70 spots representing different protein forms from which only some of them were identified at the protein species level.

7p inspiron33 26-03-2013 39 4   Download

Serum- and glucocorticoid-induced protein kinase-1 (SGK-1) plays a crit-ical role in regulation of the epithelial sodium channel, ENaC. SGK-1 also shares significant catalytic domain homology with protein kinase B (PKB⁄AKT-1) and is a downstream effector of antiapoptotic phosphoinos-itide 3-kinase signaling.

16p inspiron33 25-03-2013 34 3   Download

We performed a functional genetic screen to find novel antiapoptotic genes that are under the regulation of the oncoprotein c-Src. Several clones were identified, including subunit S5a of the 26Sproteasome. We found that S5a rescued Saos-2 cells from apoptosis induced by Src inhibitor 4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP1).

17p galaxyss3 19-03-2013 29 2   Download

The yeast 20S proteasome is subject to sulfhydryl redox alterations, such as the oxidation of cysteine residues (Cys-SH) into cysteine sulfenic acid (Cys-SOH), followed by S-glutathionylation (Cys-S-SG). Proteasome S-glutath-ionylation promotes partial loss of chymotrypsin-like activity and post-acidic cleavage without alteration of the trypsin-like proteasomal activity.

14p galaxyss3 07-03-2013 36 5   Download

This study was undertaken to explore the potential of new therapeutic approaches designed to reactivate cell death pathways in apoptosis-refrac-tory gliomas and to characterize the underlying molecular mechanisms of this reactivation.

12p media19 06-03-2013 37 3   Download

Ubiquitination and proteasomal degradation have recently emerged as an additional level of regulation of activated forms of Rho GTPases. To char-acterize this novel regulatory pathway and to gain insight into its biological significance, we studied the ubiquitination of two constitutively activated forms of Rac1, i.e.

11p media19 05-03-2013 38 2   Download

The ubiquitin–proteasome pathway is crucial for a variety of biological processes, including spermatogenesis. Ubiquitin C-terminal hydrolase-L1 (Uch-L1) is thought to associate with monoubiquitin to control ubiquitin levels. Here, we report the identification of Uch-L1 cDNA from the testis of the rice field eel, a natural sex reversal vertebrate, by using cDNA microarray analysis.

8p media19 05-03-2013 37 3   Download