Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.25.1 (proteasome)
 28,817 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Quantitative scintigraphy of the wrist, MCP, and knee joints in patients with RA was performed using Tc-99m-MDP and Ga-67 citrate. Radiopharmaceutical uptake in affected joints was compared with uptake at 2 control reference sites (juxta-articular bone and soft tissue). Following a 6-week course of therapy with Sulindac, the patients' overall assessment of disease was improved, but the results of joint/bone and joint/soft tissue ratios were variable. Improvement using Tc-99m-MDP during the first 2 weeks of NSAID therapy was noted in the minimally inflamed wrist by joint/soft tissue measurement and in the maximally affected MCP joint by joint/bone ratio. There was no change in the joint ratios employing the Ga-67 citrate radiopharmaceutical. The initial qualitative score assigned to a joint using Tc-99m-MDP was in agreement with the calculated quantitative ratio except for the knee joint. Our results suggest that quantitative scintigraphy in its present format cannot be used as a reliable indicator to monitor the course of rheumatoid arthritis during NSAID therapy and subjective measurements are still the best judge of effective treatment.
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PMID:Quantitative scintigraphy using radiophosphate and radiogallium in patients with rheumatoid arthritis. 347 91

The vast majority of lymphocytes in vivo persist in a quiescent state. These resting lymphocytes are maintained through a cellular program that suppresses apoptosis. We show here that quiescent PBMC, but not activated PBMC or transformed lymphocytes, die in the presence of highly specific post-proline aminodipeptidase inhibitors. This form of death has the hallmarks of apoptosis, such as phosphatidylserine externalization and loss of mitochondrial transmembrane potential. However, it differs from apoptosis induced by gamma irradiation in the same cells or by Fas ligation in transformed lymphocytes in terms of caspase involvement. In addition, the aminodipeptidase inhibitor-induced cell death, but not gamma-irradiation-mediated apoptosis, can be prevented by inhibition of the proteasome complex. The target of these inhibitors is not CD26/DPPIV, but probably a novel serine protease, quiescent cell proline dipeptidase, that we have recently isolated and cloned. These studies will yield a better understanding of the requirements and the mechanisms that mediate quiescent lymphocyte homeostasis in vivo.
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PMID:A novel apoptotic pathway in quiescent lymphocytes identified by inhibition of a post-proline cleaving aminodipeptidase: a candidate target protease, quiescent cell proline dipeptidase. 1047 74

We recently isolated and cloned an intracellular post-proline cleaving aminodipeptidase, quiescent cell proline dipeptidase (QPP), which has a substrate specificity very similar to that of dipeptidyl peptidase IV (CD26/DPPIV). Highly specific inhibitors of proline aminodipeptidases activate a novel apoptotic pathway in quiescent lymphocytes. The target of these inhibitors is not CD26/DPPIV, but appears to be QPP. The apoptosis pathway induced by the aminodipeptidase inhibitors is unusual in that it is restricted to quiescent lymphocytes, but not activated or transformed lymphocytes. The caspases activated in this apoptotic pathway are different from those activated in Fas or gamma-irradiation mediated cell death pathways, and furthermore, the proteasome appears to play a role in this death pathway. A large number of signal molecules including chemokines and cytokines have a highly conserved X-Pro motif on the N-terminus, rendering them potential substrates of QPP and players in the survival of resting lymphocytes.
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PMID:Aminodipeptidase inhibitor-induced cell death in quiescent lymphocytes: a review. 1122 12

The surface presentation of peptides by major histocompatibility complex (MHC) class I molecules is critical to CD8(+) T cell-mediated adaptive immune responses. Aminopeptidases have been linked to the editing of peptides for MHC class I loading, but carboxy-terminal editing is thought to be due to proteasome cleavage. By analysis of wild-type mice and mice genetically deficient in or overexpressing the dipeptidase angiotensin-converting enzyme (ACE), we have now identified ACE as having a physiological role in the processing of peptides for MHC class I. ACE edited the carboxyl terminus of proteasome-produced MHC class I peptides. The lack of ACE exposed new antigens but also abrogated some self antigens. ACE had substantial effects on the surface expression of MHC class I in a haplotype-dependent manner. We propose a revised model of peptide processing for MHC class I by introducing carboxypeptidase activity into the process.
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PMID:The carboxypeptidase ACE shapes the MHC class I peptide repertoire. 2196 7

Transcriptional activity of nuclear receptors is the result of transactivation capability and the concentration of the receptor protein. The concentration of ecdysteroid receptor (EcR) isoforms, constitutively expressed in mammalian CHO cells, is dependent on a number of factors. As shown previously, ligand binding stabilizes receptor protein concentration. In this paper, we investigate the degradation of EcR isoforms and provide evidence that N-terminal degradation is modulated by isoform-specific ubiquitination sites present in the A/B domains of EcR-A and -B1. This was demonstrated by the increase in EcR concentration by treatment with carbobenzoxy-L-leucyl-L-leucyl-L-leucinal (MG132), an inhibitor of ubiquitin-mediated proteasomal degradation and by deletion of ubiquitination sites. In addition, EcR is degraded by the peptidyl-dipeptidase cathepsin B (CatB) and the endopeptidase cathepsin S (CatS) at the C-terminus in an isoform-specific manner, despite identical C-termini. Ubiquitin-proteasome-mediated degradation and the proteolytic action are modulated by heterodimerization with Ultraspiracle (USP). The complex regulation of receptor protein concentration offers an additional opportunity to regulate transcriptional activity in an isoform- and target cell-specific way and allows the temporal limitation of hormone action.
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PMID:N- and C-terminal degradation of ecdysteroid receptor isoforms, when transiently expressed in mammalian CHO cells, is regulated by the proteasome and cysteine and threonine proteases. 2256 80