Disease relevance of Nucb1

• Taken together, Nuc is a new kind of growth and differentiation factor associated with lupus syndrome [1].
• By using the purified protein, termed nucleobindin (Nuc), we cloned cDNA and produced recombinant(r) Nuc in Escherichia coli [2].

High impact information on Nucb1

• When overexpressed in COS-1 cells, Nuc was found to be extracellularly released [3].
• Calnuc, an EF-hand Ca(2+)-binding protein, is stored and processed in the Golgi and secreted by the constitutive-like pathway in AtT20 cells [4].
• Calnuc is an ubiquitous, EF-hand Ca(2+) binding protein found in the cytoplasm where it binds to Galphai3, in the Golgi lumen where it constitutes a Ca(2+) storage pool, and secreted outside the cell [4].
• We found by pulse-chase experiments that calnuc is synthesized in the endoplasmic reticulum, transported to the Golgi where it remains greater than 12 h and undergoes posttranslational modification (O-glycosylation and sulfation) followed by secretion into the culture medium [4].
• By immunofluorescence and immunogold labeling, endogenous calnuc is found in immature secretion granules (ISG) but not mature regulated secretory granules (RSG), whereas overexpressed calnuc-green fluorescent protein (GFP) is found in both ISG and RSG, where it colocalizes with ACTH [4].

Biological context of Nucb1

• These results suggest that Nuc is able to activate autoreactive peripheral T cells through an MHC-class II pathway leading to acceleration or induction of anti-DNA antibody production when it is excessively produced in lupus-prone mice or experimentally administered into normal mice [5].
• These results suggest that upregulation of Nuc mRNA in lymphatic organs and serum Nuc of lupus-prone mice is related to spontaneous activation of immunocompetent cells; the present data are also consistent with our previous hypothesis on the role of Nuc in the induction or enhancement of autoimmunity in lupus models of mice [6].

Anatomical context of Nucb1

• The resident Golgi protein nucleobindin and fructose-bisphosphate aldolase were preferentially associated with membranes of polarized cells, whereas alphaB crystallin was detected exclusively and in high amounts in unpolarized cells [7].
• Furthermore, antibodies against existing cytokines have so far not been shown to block Nuc activity on these B cells [1].
• Activation of autoreactive T cells that help nucleobindin-injected mice produce anti-DNA antibodies [5].
• In MRL/lpr mice, both expression of Nuc mRNA in enlarged lymph nodes and serum concentration of Nuc protein are shown to increase as disease progresses [5].

Associations of Nucb1 with chemical compounds

• Assays involving proteinase K digestion, sodium carbonate extraction and Triton X-114 extraction revealed that the insect CALNUC-like protein was a soluble protein tightly associated with the luminal surface of Golgi membranes as reported for mammalian CALNUC [8].

Other interactions of Nucb1

• The insect protein had two EF-hand loops at the same sites as the mammalian CALNUC family proteins, but had no leucine zipper which the mammalian homologues commonly have [8].
• CALNUC (nucleobindin) is localized in the Golgi apparatus in insect cells [8].

References