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Ubiquitin-dependent proteolytic systems underlie many processes, including the cell cycle, cell differentiation and responses to stress. One such system is the N-end rule pathway, which targets proteins bearing destabilizing N-terminal residues. Here we report that Ubr1p, the main recognition component of this pathway, regulates peptide import in the yeast Saccharomyces cerevisiae through degradation of Cup9p, a 35 kDa homeodomain protein. Cup9p was identified using a screen for mutants that bypass the previously observed requirement for Ubr1p in peptide import. We show that Cup9p is a short-lived protein (t1/2 approximately 5 min) whose degradation requires Ubr1p. Cup9p acts as a repressor of PTR2, a gene encoding the transmembrane peptide transporter. In contrast to engineered N-end rule substrates, which are recognized by Ubr1p through their destabilizing N-terminal residues, Cup9p is targeted by Ubr1p through an internal degradation signal. The Ubr1p-Cup9p-Ptr2p circuit is the first example of a physiological process controlled by the N-end rule pathway. An earlier study identified Cup9p as a protein required for an aspect of resistance to copper toxicity in S.cerevisiae. Thus, one physiological substrate of the N-end rule pathway functions as both a repressor of peptide import and a regulator of copper homeostasis. 相似文献
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In many metazoans, final adult size depends on the growth rate and the duration of the growth period, two parameters influenced by nutritional cues. We demonstrate that, in Drosophila, nutrition modifies the timing of development by acting on the prothoracic gland (PG), which secretes the molting hormone ecdysone. When activity of the Target of Rapamycin (TOR), a core component of the nutrient-responsive pathway, is reduced in the PG, the ecdysone peak that marks the end of larval development is abrogated. This extends the duration of growth and increases animal size. Conversely, the developmental delay caused by nutritional restriction is reversed by activating TOR solely in PG cells. Finally, nutrition acts on the PG during a restricted time window near the end of larval development that coincides with the commitment to pupariation. In conclusion, the PG uses TOR signaling to couple nutritional input with ecdysone production and developmental timing. 相似文献
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Negative regulation of the Wnt-beta-catenin pathway by the transcriptional repressor HBP1 总被引:1,自引:0,他引:1
Sampson EM Haque ZK Ku MC Tevosian SG Albanese C Pestell RG Paulson KE Yee AS 《The EMBO journal》2001,20(16):4500-4511
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TEL is a sequence-specific transcriptional repressor. 总被引:6,自引:0,他引:6
R G Lopez C Carron C Oury P Gardellin O Bernard J Ghysdael 《The Journal of biological chemistry》1999,274(42):30132-30138
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GDNF-inducible zinc finger protein 1 is a sequence-specific transcriptional repressor that binds to the HOXA10 gene regulatory region 下载免费PDF全文
Morinaga T Enomoto A Shimono Y Hirose F Fukuda N Dambara A Jijiwa M Kawai K Hashimoto K Ichihara M Asai N Murakumo Y Matsuo S Takahashi M 《Nucleic acids research》2005,33(13):4191-4201
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