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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

A new functional screening system for identification of regulators for the generation of amyloid beta-protein.

Presenilin ( PS) is essential for gamma-cleavage, which is required for the generation of amyloid beta-protein ( Abeta) from the beta-amyloid precursor protein. However, it remains to be clarified how gamma-cleavage is regulated. To elucidate the regulation of PS-mediated gamma-cleavage, we developed a new functional screening method for identifying cDNA that enhances gamma-cleavage. This screening system utilizes our own developed cell line, where the expression of cDNA that enhances gamma-cleavage confers puromycin resistance. The cDNA library is retrovirally delivered to the above-mentioned cell line, allowing the identification of our target cDNAs by a combination of puromycin resistance selection and Abeta assay screening. With this screening method, we isolated several cDNAs enhancing gamma-cleavage, including the previously reported Herp. Here we also demonstrate that Rab1A, identified with this screening, can be a regulator of Abeta generation. Thus, our established screening method is a powerful tool for identifying multiple regulators involved in gamma-cleavage in the Abeta generation pathway, including modulators of gamma-secretase activity or the intracellular trafficking of factors necessary for gamma-cleavage.[1]

References

  1. A new functional screening system for identification of regulators for the generation of amyloid beta-protein. Komano, H., Shiraishi, H., Kawamura, Y., Sai, X., Suzuki, R., Serneels, L., Kawaichi, M., Kitamura, T., Yanagisawa, K. J. Biol. Chem. (2002) [Pubmed]
 
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