Disease relevance of Ubr1

• Loss or reduced levels of Ubr1 expression was associated with 5/14 spontaneous B-cell lymphomas in IgHmu-HOX11(Tg) mice and one of nine primary human T-ALLs [1].

High impact information on Ubr1

• In addition, we found that Ubr1(-/-) mice, whose previously reported phenotypes include reduced weight and behavioral abnormalities, had an exocrine pancreatic insufficiency, with impaired stimulus-secretion coupling and increased susceptibility to pancreatic injury [2].
• Ubr1 is ubiquitously expressed in adults, with skeletal muscle and heart being the sites of highest expression [3].
• Mouse Ubr1 spans approximately 120 kilobases of genomic DNA and contains approximately 50 exons [3].
• In mouse embryos, the Ubr1 expression is highest in the branchial arches and in the tail and limb buds [3].
• Ubr1 is located in the middle of mouse chromosome 2 and in the syntenic 15q15-q21.1 region of human chromosome 15 [3].

Biological context of Ubr1

• Finally, mitotic figures analysed from Ubr1 siRNA-transfected fibroblast cultures revealed no defects in chromosome congression to the metaphase plate, but increased incidences of atypical anaphase figures, including the development of anaphase bridges and lagging chromosomes [1].
• Loss of Ubr1 promotes aneuploidy and accelerates B-cell lymphomagenesis in TLX1/HOX11-transgenic mice [1].
• Proviral insertional mutagenesis studies performed on transgenic mice ectopically expressing TLX1/HOX11 in B lymphocytes (IgHmu-HOX11(Tg) mice) revealed the Ubr1 gene locus as a frequent site of proviral insertion, concomitant with accelerated development of diffuse large B-cell lymphoma [1].
• Moreover, micronucleus assays to detect for chromosome missegregation were conducted and revealed increased presence of micronuclei in IgHmu-HOX11(Tg)/Ubr1(-/-) primary B lymphocyte cultures, and in both TLX1/HOX11-overexpressing T cell lines and fibroblast cultures following transfection with short interfering RNAs (siRNAs) targeting Ubr1 [1].

Associations of Ubr1 with chemical compounds

• N-terminal arginine of a substrate protein is bound by the Ubr1-encoded E3alpha, the E3 component of the ubiquitin-proteasome-dependent N-end rule pathway [4].

Analytical, diagnostic and therapeutic context of Ubr1

• Western immunoblot and semiquantitative reverse transcriptase-PCR analysis revealed downregulated expression of the Ubr1 gene product subsequent to viral integration [1].

References