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J. Biol. Chem., Vol. 280, Issue 47, 39268-39272, November 25, 2005

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Saitohin, Which Is Nested in the tau Locus and Confers Allele-specific Susceptibility to Several Neurodegenerative Diseases, Interacts with Peroxiredoxin 6^*

Lei Gao, Sze-Wah Tse, Christopher Conrad, and Athena Andreadis¶1

From the Shriver Center at University of Massachusetts Medical School, Waltham, Massachusetts 02452, the Massachusetts General Hospital, Department of Neurology/Alzheimer's Unit, Charlestown, Massachusetts 02129, and the ^¶Department of Cell Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01655

Saitohin is a gene unique to humans and their closest relatives, the function of which is not yet known. Saitohin contains a single polymorphism (Q7R), and its Q and R alleles belong to the H1 and H2 tau haplotype, respectively. The Saitohin Q allele confers susceptibility to several neurodegenerative diseases. To get a handle on Saitohin function, we used it as a bait in a yeast two-hybrid screen. By this assay and subsequent co-immunoprecipitation and glutathione S-transferase pull-down assays, we discovered and confirmed that Saitohin interacts with peroxiredoxin 6, a unique member of that family that is bifunctional and the levels of which increase in Pick disease. The strength of the interaction appeared to be allele-specific, giving the first distinction between the two forms of Saitohin.

Received for publication, June 6, 2005 , and in revised form, August 19, 2005.

^* This study was supported by NIA, National Institutes of Health, Grant AG018486 (to A. A.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence may be addressed: Shriver Center, 200 Trapelo Rd., Waltham, MA 02452. Tel.: 781-642-0279; Fax: 781-642-0017; E-mail: athena.andreadis{at}umassmed.edu.

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