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

The lymphocyte cell surface receptor for the high endothelial venules (HEV's) of peripheral lymph nodes is specifically recognized by the monoclonal antibody MEL-14. Three independent complementary DNA (cDNA) clones, each of which encodes the protein ubiquitin, were detected by virtue of the expression of the MEL-14 antigenic determinant on cDNA-beta-galactosidase bacterial fusion proteins. The antigenic determinant defined by MEL-14 resides in the carboxyl terminal 13-amino-acid proteolytic peptide of ubiquitin, but is undetected in intact undenatured ubiquitin and other cellular ubiquitinated proteins. Antisera and monoclonal antibodies to ubiquitin determinants bind to the surface of both HEV-receptor positive and negative cell lines. The MEL-14-identified cDNA clones hydridize to RNA transcripts that encode tandemly repeated ubiquitins. Sequence analysis of these polyubiquitin cDNA's does not identify a leader sequence for export to the cell surface. The expression of the MEL-14 epitope of ubiquitin depends upon its local environment. The steady-state levels of expression of the ubiquitin messenger RNA's do not correlate with either the tissue derivation of the RNA or the expression of the lymphocyte HEV receptor. Regulation of the expression of the HEV receptor is not likely to reflect the transcriptional control of ubiquitin genes, but rather to reflect control of the expression of the HEV core polypeptide or its level or form of ubiquitination.
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PMID:Expression cloning of a lymphocyte homing receptor cDNA: ubiquitin is the reactive species. 300 14

Ubiquitin is a highly conserved protein involved in many important cellular processes, such as cell surface receptor signaling, endocytosis and protein degradation. Since ubiquitin plays a key role in the pathomechanisms of many neurodegenerative diseases, we immunohistochemically analyzed its expression in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). CADASIL is a heritable vascular dementia characterized by degeneration of the vascular smooth muscle cells (VSMC) caused by mutations in the notch 3 gene. In CADASIL, there is abnormal accumulation of the Notch 3 extracellular domain on blood vessels, but the molecular pathways linking notch 3 mutations to degeneration of the VSMC are, as yet, poorly understood. We studied human brain and skin biopsy specimens, and observed increased ubiquitin expression on structures primarily affected by the pathological process in CADASIL: the VSMC and vascular lamina media, and also large ballooned macrophages. Ultrastructurally, we noted that pathognomonic CADASIL deposits of granular osmiophilic material were often located inside indentations in the VSMC membrane that resembled endocytic vesicles. We suggest that in CADASIL, damage to the VSMC may be associated with aberrant ubiquitin-dependent endocytosis of the Notch 3 ligand, and increased accumulation of ubiquitin on the vessel wall may be a manifestation of this aberration.
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PMID:Is the increased expression of ubiquitin in CADASIL syndrome a manifestation of aberrant endocytosis in the vascular smooth muscle cells? 1831