Fig. 7. (A-C) The model for the downregulation of YAN. (D,E) The model for the activation and subsequent downregulation of PNT-P2. (A) In the absence of signaling, YAN localizes to DNA, repressing transcription. (B) Upon RTK signaling, phosphorylated MAPK enters the nucleus, interacts with YAN-MAE complex and phosphorylates YAN. YAN is removed from the DNA, although the exact timing of this event is not yet clear. (C) The YAN-MAE complex then interacts with CRM1, causing release of MAE and CRM1 mediated export of YAN through the nuclear pore. (D) In the absence of signaling, PNT-P2 can bind to MAE and is prevented from activating transcription, either as a consequence of its interaction with MAE or because it is out competed by YAN, or both. (E) Upon RTK activation, phosphorylated MAPK enters the nucleus and phosphorylates PNT-P2. This allows PNT-P2 to bind DNA and activate transcription of the target genes now freed from YAN repression. (F) To prevent runaway signaling, a negative feedback loop may occur in which MAE binds to PNT-P2 and inhibits transcriptional activation. This could occur by MAE binding causing PNT-P2 to no longer bind DNA (1), or by MAE binding resulting in dephosphorylation of PNT-P2 (2), resulting in inhibition of transcriptional activation.

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