Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P62988 (Ubiquitin)
 4,326 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ubiquitin (Ub), a stress protein thought to target abnormal proteins for degradation, is present in abnormal structures that occur in neuronal perikarya and axons of degenerative diseases including Alzheimer disease. To begin to assess the role of the Ub system in the axon, we studied expression and axonal transport of Ub and other stress proteins, as well as of Ub carboxyl-terminal hydrolase PGP 9.5, in the rat visual system in normal conditions and following heat-shock (HS). In the retina, both the constitutive and inducible forms of HSPs 70 were expressed under normal conditions, while in the superior colliculus the inducible form was detected only following HS. Ub, PGP 9.5 and HSPs 70 were transported in the axon exclusively with the slow component b (SCb), known to carry cytoskeletal and cytoplasmic proteins. The exceedingly long time needed for stress proteins to reach distant axonal locales at the rate of SCb (approximately 3 mm/day) makes it unlikely that they could contribute significantly to the stress response at those sites.
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PMID:Axonal transport of two major components of the ubiquitin system: free ubiquitin and ubiquitin carboxyl-terminal hydrolase PGP 9.5. 171 33

The heat shock/stress response is characterized by the induction of several highly evolutionarily conserved proteins during thermal stress, chemical stress, or glucose starvation. It has recently been recognized that members of the stress protein family are synthesized constitutively and subserve functions that are critical to protein folding during intracellular transport. In this study we examined the expression of heat shock/stress proteins in human mononuclear phagocytes, cells dependent on intracellular transport for Ag processing, Ag presentation, generation of reactive oxygen intermediates, and secretion of proinflammatory and antiinflammatory polypeptides. The results indicate that there are distinct patterns in expression of individual members of the highly homologous SP70, SP90, and ubiquitin gene families during different stress states. There is a marked increase in expression of the heat-inducible form of SP70 and SP90 in human monocytes during heat shock. Expression of GRP 78/BiP and GRP 94 increases predominantly during glucose starvation but also increases during heat shock. Ubiquitin gene expression increases during both heat shock and glucose starvation. There is no change in synthesis of the constitutive form of SP 70 or of the ubiquitin activating enzyme E1 during heat shock or glucose starvation. Synthesis of the constitutive form of SP 70 and novel SP 90-like polypeptides increase during endotoxin-mediated inflammatory activation. One intracellular transport process of the mononuclear phagocyte, secretion of specific proinflammatory and antiinflammatory polypeptides, is affected by glucose starvation and by heat shock.
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PMID:Expression of stress proteins in human mononuclear phagocytes. 188 Apr 18

Inclusions containing ubiquitin-protein aggregates appear in neurons of patients with neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. The relationship between inclusion production and cell viability is not understood. To address this issue, we investigated the response of an established mouse neuronal cell line and of embryonic rat mesencephalic cultures to inhibition of the ubiquitin/proteasome pathway. Two proteasome inhibitors, a peptidyl aldehyde and an epoxy ketone, which cause accumulation of ubiquitinated proteins, were found to enhance expression of stress-inducible genes, including HSP70i and the polyubiquitin genes UbB and UbC. Under these conditions, mRNA and protein levels of the inducible form of cyclooxygenase (COX-2) were upregulated together with its product, PGE(2), a proinflammatory prostaglandin. Proteasomal inhibition also led to stabilization of COX-2 as ubiquitin conjugates, suggesting that the ubiquitin/proteasome pathway contributes to the regulation of COX-2 protein levels. Treatment with antioxidants known to inhibit NFkappaB and AP-1 transcriptional activation failed to abrogate COX-2 upregulation. Instead, these inhibitors exacerbated the stress response by potentiating HSP70i levels while eliciting a decrease in PGE(2) production. These findings suggest that the accumulation of ubiquitinated proteins resulting from proteasome inhibition in neuronal cells is associated with a proinflammatory response that may be an important contributor to neurodegeneration.
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PMID:Proteasome inhibition in neuronal cells induces a proinflammatory response manifested by upregulation of cyclooxygenase-2, its accumulation as ubiquitin conjugates, and production of the prostaglandin PGE(2). 1066 14