Anti-UBA52: Mouse UBA52 Antibody

BACKGROUND The ubiquitin (Ub)-proteasome system is the major non-lysosomal proteolytic pathway in eukaryotes. Proteins are targeted for destruction by the addition of poly-Ub chains to a lysine residue of the substrate proteins. Although ubiquitin has no intrinsic proteolytic activity, it plays an important role in the turnover of cellular proteins by closely regulating their degradation. The latter is a multistep ATP-dependent pathway that involves the activation of carboxyl terminus of ubiquitin, its conjugation with a specific protein, and the addition of ubiquitins to form polyubiquitin, which is involved in E1 (Ub-activating enzyme), E2 (Ub-conjugating enzyme), and E3 (Ub-ligase) and is then followed by degradation of ubiquitin-tagged protein in 26S proteasome with the release of peptide fragments of the protein and ubiquitin to be reutilized. The ubiquitin gene typically exists in two states. First, as a doublet, e.g. ubiquitin B, or linear repeats in a polyubiquitin chain, i.e. ubiquitin C; second, the ubiquitin gene may be fused to ribosomal proteins, i.e. UbA52 and UbA80. The ubiquitin-dependent proteolysis is responsive to the stimuli of a diverse group of molecules and the ubiquitin-dependent proteolytic pathway is relevant in various biological processes.¹

UbA52 is a 128-amino acid ubiquitin fusion protein and is made up of a 52-amino acid 60 S ribosomal protein attached to a 76-amino acid ubiquitin peptide. The ubiquitin is highly conserved in various species and is generated in cells by proteolysis of larger proteins containing either polyubiquitin chains or ubiquitin fused to carboxyl extension proteins. In humans, two ubiquitin-carboxyl extension protein genes, UbA80 and UbA52, code for ubiquitin fused to ribosomal proteins S27a and L40, respectively. The mouse UbA52 protein sequence was identical to that of the human and also of the UbA80 up to the 60th amino acid residue. It was demonstrated that UbA52 is relevant to the pathobiology of diabetic nephropathy, and its transcription regulation is modulated by the characteristic elements embedded in its promoter region. Its mRNA expression in the kidney was proportional to blood glucose levels.² As known, the molecular mechanisms for ubiquitinated protein sorting to the proteasome rely on a cooperation of chaperone machineries and ubiquitin-chain recognition factors. The isoforms of the Hsc70 cochaperone HSJ1 are key components in neuronal protein unquality control. Human HSJ1a and HSJ1b both belong to the family of J-proteins that stimulate ATP hydrolysis by Hsc70. On the basis of this Hsc70-regulating activity and an intrinsic chaperone function, HSJ1 isoforms facilitate substrate loading onto Hsc70. It was shown that both UbA80 and UbA52 are binding partners of the cochaperone. There are two ubiquitin interaction motif (UIM) domains within the primary structure of both cochaperone isoforms. HSJ1 prevents client aggregation, shields clients against chain trimming by ubiquitin hydrolases, and stimulates their sorting to the proteasome. In this way, HSJ1 isoforms participate in ER-associated degradation (ERAD) and protect neurons against cytotoxic protein aggregation.³
 

REFERENCES  

1. Hochstrasser, M.: Nature 458: 422-9, 2009
2. Sun, L. et al: J. Biol. Chem. 277:29953-62, 2002
3. Westhoff, B. et al: Curr. Biol. 15:1058-64, 2005