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Proteasomes.com is a division of A. G. Scientific. Inc.

The scientific resource for elucidating the Ubiquitin / Proteasome Pathway. Proteasomes.com provides innovative, research chemicals including: Proteasome Inhibitors, Substrates, Enzymes, and Antibodies to assist you in understanding the importance of this pathway.

AGScientific partners with Proteome Resources LLC

Overview

Protein homeostasis is a complex and essential process in all living cells. The vast majority of cellular proteins not targeted for lysosomal degradation in eukaryotes are processed and degraded by the 26S proteasome (multicatalytic proteinase complex, prosome). Thus, the proteasome is implicated in numerous, important biological functions. The disruption or corruption of this process can have deleterious effects on cell growth and viability and lead to a variety of human diseases.

The proteasome is large, multimeric protein (~2.5 Mda, approx. 30 subunits; regulatory and catalytic) It is a processing molecular machine found in diverse organisms from yeast to humans. Given this level of evolutionary conservation it is not surprising that similar structures also are found in bacteria and archae. The proteasome is responsible for removing damaged, misfolded, nonfunctional and potentially toxic proteins from the cell. Loss of proteasomal activity is associated with cellular aging.

Protein degradation via the ubiquitin/proteasome pathway involves two successive steps. The first step is the enzymatic attachment of multiple ubiquitin molecules to the target protein followed by proteolysis of the ubiquitin-protein conjugate by the 26S proteasome complex. Proteolysis via the ubiquitin-proteasome pathway is distinct and regulated differently than either apoptosis (programmed cell death requiring caspases), or lysosomal protein degradation.

Studies have revealed that the proteasome is intimately involved in regulating numerous cellular processes. These are known to include mitosis, cellular differentiation, signal transduction, modulation of immune and inflammatory responses, transcriptional activation, DNA repair, chromosome maintenance, and apoptosis. For example, positive and negative regulators of apoptosis and cell division are subject to proteasomal degradation in a temporally and highly restrained way, thus illustrating the ability of the proteasome to assume two roles in Cellular apoptosis and proliferation.

The variety of human diseases that can be traced to malfunctioning ubiquitin/proteasome process is significant and diverse. Cancer arising from defective proto-oncogene expression patterns can, in many cases, be traced to a flawed proteasome degradation profile of members belonging to this group. Numerous neurodegenerative diseases including Alzheimer's, Parkinson's, Huntington's, amyolateral lateral sclerosis and spongiform encephalopathies (Mad Cow) also can be linked to faulty proteasomal degradation of specific proteins. Some inflammatory and auto-immune diseases also arise due to inappropriate proteasome pathway activity.

The proteasome-mediated protein degradation pathway is of such significance in various intracellular processes that specific tools are required to elucidate the involvement of the Ubiquitin / Proteasome pathway. Proteasomes.com has sought to provide the absolute newest & most specific reagents to this field. We look forward to aiding your discoveries.

Recent Reviews

  1. The proteasome system and proteasome inhibitors in stroke: controlling the inflammatory response. Di Napoli M, Papa F. Curr Opin Investig Drugs. 2003 Nov;4(11):1333-42.
  2. Deconstructing the axon: Wallerian degeneration and the ubiquitin-proteasome system. Ehlers MD. Trends Neurosci. 2004 Jan;27(1):3-6.
  3. Apoptosis meets proteasome, an invaluable therapeutic target of anticancer drugs. Giuliano M, D'Anneo A, De Blasio A, Vento R, Tesoriere G. Ital J Biochem. 2003 Jun;52(2):112-21.
  4. The diverse roles of ubiquitin and the 26S proteasome in the life of plants. Sullivan JA, Shirasu K, Deng XW. Nat Rev Genet. 2003 Dec;4(12):948-58.
  5. Interruption of tumor cell cycle progression through proteasome inhibition: implications for cancer therapy. Dou QP, Smith DM, Daniel KG, Kazi A. Prog Cell Cycle Res. 2003;5:441-6.
  6. The ubiquitin proteasome system in neurodegenerative diseases: sometimes the chicken, sometimes the egg. Ciechanover A, Brundin P. Neuron. 2003 Oct 9;40(2):427-46.
  7. The proteasome: a novel therapeutic target in haematopoietic malignancy. Magill L, Walker B, Irvine AE. Hematology. 2003 Oct;8(5):275-83.
  8. The role of the ubiquitin/proteasome system in cellular responses to radiation. McBride WH, Iwamoto KS, Syljuasen R, Pervan M, Pajonk F. Oncogene. 2003 Sep 1;22(37):5755-73.
  9. Does proteasome inhibition play a role in mediating neuropathology and neuron death in Alzheimer's disease? Ding Q, Keller JN. J Alzheimers Dis. 2003 Jun;5(3):241-5.
  10. Proteolysis, the ubiquitin-proteasome system, and renal diseases. Debigare R, Price SR. Am J Physiol Renal Physiol. 2003 Jul;285(1):F1-8.
  11. Therapeutic anti-cancer targets upstream of the proteasome. Nalepa G, Wade Harper J. Cancer Treat Rev. 2003 May;29 Suppl 1:49-57.
  12. Rationale for the treatment of solid tumors with the proteasome inhibitor bortezomib. Cusack JC. Cancer Treat Rev. 2003 May;29 Suppl 1:21-31.
  13. Clinical update: proteasome inhibitors in solid tumors. Lenz HJ. Cancer Treat Rev. 2003 May;29 Suppl 1:41-8.
  14. The proteasome: structure, function, and role in the cell. Adams J. Cancer Treat Rev. 2003 May;29 Suppl 1:3-9.
  15. Assays for proteasome inhibition. Elliott PJ, Soucy TA, Pien CS, Adams J, Lightcap ES. Methods Mol Med. 2003;85:163-72.
  16. Proteasome inhibition: a new anti-inflammatory strategy. Elliott PJ, Zollner TM, Boehncke WH. J Mol Med. 2003 Apr;81(4):235-45. Epub 2003 Mar 26.
  17. The components of the proteasome system and their role in MHC class I antigen processing. Kruger E, Kuckelkorn U, Sijts A, Kloetzel PM. Rev Physiol Biochem Pharmacol. 2003;148:81-104. Epub 2003 Mar 25.
  18. Regulation of membrane protein transport by ubiquitin and ubiquitin-binding proteins. Hicke L, Dunn R. Annu Rev Cell Dev Biol. 2003;19:141-72.
  19. Non-traditional functions of ubiquitin and ubiquitin-binding proteins. Schnell JD, Hicke L. J Biol Chem. 2003 Sep 19;278(38):35857-60. Epub 2003 Jul 14.
  20. Orchestrating nuclear functions: ubiquitin sets the rhythm. Bach I, Ostendorff HP. Trends Biochem Sci. 2003 Apr;28(4):189-95.

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