Disease relevance of UBB

• BACKGROUND & AIMS: Molecular misreading of the ubiquitin B gene has been documented in the cerebral cortex of patients with Alzheimer's disease and Down syndrome [1].
• Molecular misreading was discovered in the rat vasopressin gene associated with diabetes insipidus and subsequently in human genes linked to Alzheimer's disease (AD), e.g. beta amyloid precursor protein (betaAPP) and ubiquitin-B (UBB) [2].
• Because SMECE often occur in glands with chronic lymphocytic thyroiditis and UBB hyperplasia, and do not stain like follicular or parafollicular cells, it is likely that the tumors do arise from UBB/solid cell nests [3].
• This is expressed by hyperplasia of follicular cells, formation of secondary follicles and increased vascular supply to the UBB [4].
• Aberrant forms of proteins ubiquitin B and beta-amyloid precusor protein, UBB+1 and APP+1, are implicated in human neurodegenerative diseases [5].

Psychiatry related information on UBB

• Here frame-shift ubiquitin-B and amyloid precursor protein were immunochemically shown to exist in the brain of high pathology control (HPC) patients with AD pathology but without prior dementia [6].

High impact information on UBB

• Frameshift mutants of beta amyloid precursor protein and ubiquitin-B in Alzheimer's and Down patients [7].
• CONCLUSIONS: The results showed that molecular misreading of the ubiquitin B gene occurred in hepatocytes in virtually all of the MB-containing livers tested [1].
• Recently, the deposits have been shown to contain protein fragments of ubiquitin-B and amyloid precursor protein (APP) with an aberrant carboxyl terminus resulting from frameshift mutations (dinucleotide deletions; DeltaGU or DeltaGA) in or adjacent to GAGAG motifs in their mRNAs, a process referred to as molecular misreading [8].
• Appending a portion of the CMV enhancer 5' of the UBB promoter (CMV-Ub) increased CAT expression to nearly that of the CMV promoter and expression persisted in the lung for at least 3 months, with 50% of day 2 levels remaining at day 84 [9].
• Chloramphenicol acetyltransferase (CAT) reporter gene expression from the UBB promoter was initially very low at day 2 post-administration, but by day 35 exceeded the level of expression attained from a CMV promoter vector by four- to ninefold [9].

Biological context of UBB

• The UBB and UBC polyubiquitin genes have previously been mapped by the use of specific intron or 5' flanking sequence probes [10].
• Novel frameshift mutations at a number of locations in the transcripts of the ubiquitin-B and APP genes were discovered (DeltaGA, DeltaG, DeltaGU, DeltaGG, DeltaCA, DeltaAU, DeltaA, DeltaAA, DeltaC, DeltaU, and insertion of an A) [8].

Anatomical context of UBB

• Furthermore, the etiology of these tumors has been debated in the literature, with some authors believing that the tumors arise from remnants of the ultimobranchial body (UBB, solid cell nests) and others proposing that they arise from follicular epithelial cells [3].
• Neurofibrillary tangles in progressive supranuclear palsy brains exhibit immunoreactivity to frameshift mutant ubiquitin-B protein [11].

Associations of UBB with chemical compounds

• In N. notopterus the effects of hypercalcaemia (caused by keeping the specimens in 0.5% of CaCl2 solution and by injecting 4000 I.U. of vitamin D2 on alternate days) on UBB has been observed [12].

Other interactions of UBB

• In this study, we provide additional evidence for this relationship, by demonstrating that SMECE stain strongly positive for p63, which is a new marker for UBB/solid cell nests [3].

References