Disease relevance of NUB1

• In this study, we immunostained sections of brains from patients with Parkinson's disease and other alpha-synucleinopathies and demonstrated that NUB1, as well as synphilin-1, accumulates in the inclusion bodies [1].

High impact information on NUB1

• This assay showed that NUB1 suppresses the formation of synphilin-1-positive inclusions [1].
• To define the role of NUB1 in the formation of these inclusion bodies, we performed a co-transfection assay using cultured HEK293 cells [1].
• AIPL1 interacts with the cell cycle regulator NEDD8 ultimate buster protein 1 (NUB1) [2].
• Because NUB1 was shown to bind to the proteasome subunit RPN10 in vitro and to be contained in 26 S proteasome preparations, it may function as a linker that targets FAT10 for degradation by the proteasome [3].
• Structural study revealed that NUB1 has a NEDD8-binding site at the C terminus, whereas NUB1L has an additional site at the newly generated UBA domain [4].

Biological context of NUB1

• These data show that AIPL1 can modulate protein translocation and act in a chaperone-like manner and suggest that AIPL1 is an important modulator of NUB1 cellular function [2].
• These results may imply that the UbC1 hydrolysis mediated by NUB1 is involved in cellular functions in the seminiferous tubules such as spermatogenesis [5].
• Furthermore, proteasome inhibitors completely block NUB1-mediated down-regulation of NEDD8 expression [6].
• METHODS: Additional genetic screening was performed and the consequences of the H82Y amino acid substitution characterized in an in vitro assay of NUB1 modulation [7].
• RESULTS: Transfection of the H82Y mutant AIPL1 in SK-N-SH cells revealed a normal subcellular localization and solubility but resulted in an increased ability of AIPL1 to redistribute GFP-NUB1 to the cytoplasm and resolve NUB1 fragment inclusion formation [7].

Anatomical context of NUB1

• Northern blot analysis showed that the mRNAs of both NUB1 and UbC1 were enriched in the testis [5].
• NUB1 was localized in cell nuclei throughout the human fetal and adult eye at all time points [8].
• The growth of the cultured human breast carcinoma cell line NUB 1 as well as that of other cultured malignant cells has been shown to be inhibited by addition of gamma-linolenic acid (GLA) to the culture medium [9].

Associations of NUB1 with chemical compounds

• To test this hypothesis the effect of 50 micrograms/ml concentrations of GLA and its sequential metabolite dihomo-gamma-linolenic acid (DGLA) and cell growth, morphology and prostaglandin (PGE and PGF) production by NUB 1 cells was investigated [9].

Physical interactions of NUB1

• NUB1 interacts with a ubiquitin-like protein NEDD8 to target the NEDD8 monomer and neddylated proteins to the proteasome for degradation [10].

Regulatory relationships of NUB1

• Interestingly, AIPL1 was able to act in a chaperone-like fashion to efficiently suppress inclusion formation by NUB1 fragments [2].

Other interactions of NUB1

• We examined the effect of a range of pathogenic and engineered mutations on the ability of AIPL1 to modulate NUB1 localization or inclusion formation [2].
• Abolished interaction of NUB1 with mutant AIPL1 involved in Leber congenital amaurosis [11].
• We review the evidence for the role of AIP in protein translocation and compare the potential functions of AIPL1 in the translocation of its interacting partner the NEDD8 ultimate buster protein 1 [12].

Analytical, diagnostic and therapeutic context of NUB1

• The spatiotemporal distribution of NUB1 was also examined by immunohistochemistry, using a newly developed anti-serum to the C terminus of NUB1 [8].

References