Proteasome Endopeptidase Complex (Proteasome)

A large multisubunit complex that plays an important role in the degradation of most of the cytosolic and nuclear proteins in eukaryotic cells. It contains a 700-kDa catalytic sub-complex and two 700-kDa regulatory sub-complexes. The complex digests ubiquitinated proteins and protein activated via ornithine decarboxylase antizyme.

Also Known As:

Networked: 5494 relevant articles (251 outcomes, 679 trials/studies)

Relationship Network

Bio-Agent Context: Research Results

Experts

1.	Dou, Q Ping: 104 articles (12/2015 - 07/2002)
2.	Anderson, Kenneth C: 69 articles (06/2015 - 05/2002)
3.	Orlowski, Robert Z: 41 articles (03/2015 - 08/2002)
4.	Richardson, Paul G: 39 articles (06/2015 - 06/2002)
5.	Wang, Xuejun: 38 articles (08/2015 - 09/2004)
6.	Hideshima, Teru: 36 articles (04/2014 - 05/2002)
7.	Chen, Di: 34 articles (08/2014 - 01/2004)
8.	Chauhan, Dharminder: 32 articles (03/2014 - 05/2002)
9.	Yang, Huanjie: 24 articles (12/2015 - 05/2006)
10.	Liu, Jinbao: 22 articles (08/2015 - 09/2004)

Related Diseases

1.	Multiple Myeloma 01/01/2015 - "Despite the fact that multiple myeloma (MM) is still an incurable disease, the outcome of patients who are eligible and ineligible for high-dose therapy has dramatically improved with the introduction of novel agents, that is proteasome inhibitors (PIs) and immunomodulatory agents (IMiDs). " 01/01/2014 - "Inhibition of the proteasome has proven very effective in the treatment of multiple myeloma, and this approach is being tested for utility in other malignancies. " 01/01/2016 - "The development of proteasome inhibitors (PIs) and immunomodulatory drugs has significantly improved outcomes for patients with relapsed/refractory multiple myeloma (RRMM); however, not all patients benefit from treatment with these agents and some patients can become drug refractory over time. " 11/01/2015 - "Over the past decade, use of novel agents, including immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs) has resulted in high response rates and improvement in overall survival (OS) for patients with multiple myeloma (MM); however, the prognostic significance of refractoriness to these agents when used as initial therapy has not been extensively studied. " 10/01/2013 - "The outlook for patients with multiple myeloma (MM) has improved significantly with the development of new and more effective therapies, particularly the immunomodulatory agents and proteasome inhibitors. "
2.	Neoplasms (Cancer) 01/01/2014 - "However, proteasome inhibitors have not proved effective in treating other cancers, and this has called into question the general applicability of this approach. " 03/15/2012 - "Proteasome inhibition is effective in reducing cell growth and inducing apoptosis of ATC in vitro and inhibiting tumor growth and vascularity in vivo. " 10/15/2010 - "Thus, proteasome inhibition is effective in killing tumor cells within the bone. " 12/01/2008 - "Proteasome inhibition is effective in treating certain forms of cancer, while UPS dysfunction is increasingly implicated in the pathogenesis of many severe and yet common diseases. " 12/01/2008 - "These results suggest that strategies targeting the conditional proteasome-mediated destruction of tumor cell EphA2 may enable EphA2-specific CD8(+) T cells (of modest functional avidity) to realize improved therapeutic potential."
3.	Hematologic Neoplasms (Hematological Malignancy) 03/01/2008 - "Proteasome inhibitors are proving to be of significant value in the treatment of hematologic malignancies and these observations may help to better understand the biology of therapy with these compounds." 03/01/2013 - "Proteasome inhibition has been recognized as a novel treatment modality in hematologic malignancies. " 04/01/2012 - "Proteasome inhibition is a novel treatment for several hematological malignancies. " 04/10/2014 - "Selective inhibitors for the human immunoproteasome LMP7 (β5i) subunit over the constitutive proteasome hold promise for the treatment of autoimmune and inflammatory diseases and hematologic malignancies. " 06/01/2015 - "Phase 1 study of ixazomib, an investigational proteasome inhibitor, in advanced non-hematologic malignancies."
4.	Neurodegenerative Diseases (Neurodegenerative Disease) 01/01/2015 - "The UPS is reportedly downregulated in various neurodegenerative disorders, with increased proteasome activity shown to be beneficial in many related disease models. " 08/15/2012 - "Our results suggest that proteasomal activation may not always be beneficial for alleviating neurodegeneration and that blocking the proteasome may represent a potential therapeutic avenue for treating some forms of neurodegenerative disease." 08/01/2012 - "At variance with other inclusion bodies linked to neurodegenerative diseases, clearance of P56S-VAPB inclusions involves the proteasome, with no apparent participation of macro-autophagy. " 01/01/2014 - "Taken together, this study suggests that a decrease in proteasome activity can, through activation of c-Jun and ERK 1/2, result in several events related to neurodegenerative diseases. " 12/01/2002 - "Some recent studies reported that a proteasome dysfunction was involved in the pathogenesis of neurodegenerative diseases. "
5.	Peripheral Nervous System Diseases (PNS Diseases) 03/01/2008 - "These processes acting alone, or in combination, are hypothesized to affect axonal transport or other aspects of cellular homeostasis and thus, represent events potentially relevant to the development of peripheral neuropathy associated with administration of proteasome inhibitors in nonclinical studies." 10/01/1999 - "Together, these studies suggest that the proteasome pathway is critical for the regulation of PMP22 protein levels and raise the possibility that aggresomes may be involved in the pathogenesis of PMP22-associated peripheral neuropathies." 01/01/2015 - "[Management of proteasome inhibitor-induced peripheral neuropathy]." 12/01/2014 - "Ixazomib is an investigational, oral, proteasome inhibitor with promising anti-myeloma effects and low rates of peripheral neuropathy. " 09/01/2005 - "20S proteasome levels in blood were assayed at baseline and at 1, 4, and 24 hours postdose in cycle 1. On this D1 and D4 every 2 weeks' schedule, dose-limiting toxicity (DLT) was evident at the 1.75 and 1.9 mg/m2 dose levels, most commonly in patients receiving individual total doses > or = 3.0 mg. The main DLT was peripheral neuropathy evident at the higher doses and in patients previously exposed to neurotoxic agents. "

Related Drugs and Biologics

1.	bortezomib (Velcade)
2.	lenalidomide (CC 5013)
3.	Ubiquitin
4.	Thalidomide (Thalomid)
5.	Proteins (Proteins, Gene)
6.	carfilzomib
7.	NF-kappa B (NF-kB)
8.	Histone Deacetylase Inhibitors
9.	benzyloxycarbonylleucyl-leucyl-leucine aldehyde
10.	Phosphotransferases (Kinase)

Related Therapies and Procedures

1.	Stem Cell Transplantation
2.	Drug Therapy (Chemotherapy)
3.	Therapeutics
4.	Heterologous Transplantation (Xenotransplantation)
5.	Molecular Targeted Therapy