Di/Tripeptide Uptake Is Enhanced by a Positive Feedback Loop Governed by the N-End Rule Pathway

<p>The E3 ubiquitin ligase Ubr1p contains binding sites for proteins containing Type 1 (Arg, His, and Lys) and Type 2 (Ile, Leu, Phe, Trp, and Tyr) N-terminal amino acids. In the absence of di/tripeptides, the <i>PTR2</i> repressor Cup9p is abundant and <i>PTR2</i> expression is minimal. Upon binding of Type 1 and/or Type 2 di/tripeptides to Ubr1p, an autoinhibitory domain blocking the recognition of an internal Cup9p degron dissociates from the Cup9p binding site, decreasing the half-life of Cup9p (t _½) from approximately 5 min to less than 1 min. Consequently, <i>PTR2</i> repression is relieved and elevated levels of Ptr2p enhance di/tripeptide uptake, initiating a positive feedback loop. This figure was adapted from the diagram of Turner et al. [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.0010080#pgen-0010080-b033" target="_blank">33</a>], with the authors' permission.