Serum albumin gene

Our laboratory started to work on circadian rhythms by serendipity, while studying the liver-specific transcription of the serum albumin gene. We isolated a cDN A copy for a transcription factor that we dubbed DBP (for albumin promoter D-element Binding Protein). DBP, a basic leucine zipper (bZip) transcription factor, is the founding member of the PAR (proline-acidic amino acid rich)-domain bZip transcription factors, a small subfamily of bZip proteins consisting of DBP, TEF and HLF. It turned out that DBP protein and mRNA accumulation undergo circadian cycles with amplitudes in excess of one hundred-fold (Wuarin Schibler 1990). 

Expression of the human serum albumin gene is regulated by five transcription factors, four of which bind to the promoter region. 

Mutations in a human serum albumin gene that substitute either histidine or proline for arginine at position 218 increase binding affinity for T4. These mutations are autosomal dominant and occur with relatively high frequency. Carriers of these mutations have high levels of total serum T4 but their free-T4 and TSH concentrations are within the normal range. Individuals are euthyroid (normal thyroid) and their conditions are known as familial dysalbumine-mic hyperthyroxinemia (FDH). 

Faneca H, Simoes S, Pedroso de Lima MC. Association of albumin or protamine to lipoplexes enhancement of transfection and resistance to serum. J Gene Med 2004 6 681. 

Clinical trials have demonstrated excellent efficacy with recombinant human factor VIII concentrates available as Recombinate and Kogenate. These recombinant factor VIII products are purified from the cell culture of plasmids, not viral DNA-transfected hamster cells and therefore do not express viral sequences. The addition of human serum albumin for stabilization, constitutes the sole possible source for human viral contamination. More recently recombinant factor IX has been genetically engineered by insertion of the human factor IX gene into a Chinese hamster ovary cell line. It has been proved to be safe and effective in the treatment of patients with hemophilia B. 

Rhaese, S., von Briesen, FI., Rubsamen-Waigmann, FI., Kreuter, J., and Langer, K. (2003), Human serum albumin-polyethylenimine nanoparticles for gene delivery, J. Controlled Release, 92(1-2), 199-208. 

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