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O papel modulador do gene AIRE - capes

O papel modulador do gene AIRE - capes

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<strong>gene</strong>, Prr2, (mRNA accession number NM_022999, ID 640686) and theSyntaxin binding protein 3 <strong>gene</strong>, Stxbp3, (mRNA accession numberNM_011504, ID 640484), whose respective coded proteins play a role in theinhibition of the calcium influx pathway via calcineurin, correspond to importantnodes in this and in subsequent phases.These <strong>gene</strong>s participate in the control of calcium influx pathway mediated bycalcineurin, which is important in the activation of the nuclear factor of activatedT cells (Nfat), a T cell transcription factor. As calcium signaling is implicated inthe induction of T cell anergy mediated through calcineurin and NFAT [41-43],the nodes identified could be useful to provide a clearer understanding of the<strong>gene</strong> interactions implicated in the immunological tolerance induction.Twenty-one <strong>gene</strong> nodes were identified at 14 vs 15 days p.c. and eight wereselected for discussion:1) The Prr2 is a <strong>gene</strong> node featuring self positive regulation, was positivelyregulated by 19 other <strong>gene</strong>s (of the 21 found in the network) and was indirectpositivelyregulated by two others, i.e. two <strong>gene</strong>s interacted first and thenpositively regulated the Prr2 <strong>gene</strong>; the Cope <strong>gene</strong> positively regulated thePrmt3 <strong>gene</strong>, which positively regulated the Prr2 <strong>gene</strong>: Cope → Prmt3 → Prr2.This strongly suggests the importance of maintaining the Prr2 <strong>gene</strong> transcriptionlevels. A negative feedback-like regulation, between the Prr2 <strong>gene</strong> and GolgiSNAP receptor complex 2 <strong>gene</strong>, Gosr2, (mRNA accession numberNM_019650, ID 640152) was found. While the Gosr2 <strong>gene</strong> positively regulatesPrr2, the latter presented an inhibitory effect on Gosr2.2) The Stxbp3a <strong>gene</strong> node also featured self positive regulation and waspositively regulated by three <strong>gene</strong>s participating in the network. However, this248

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