Suppressor of Deltex mediates Pez degradation and modulates Drosophila midgut homeostasis.

Suppressor of Deltex mediates Pez degradation and modulates Drosophila midgut homeostasis.
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Deltex 抑制剂介导 Pez 降解并调节果蝇中肠稳态。

DOI:
10.1038/ncomms7607
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发表时间:
2015
影响因子:
16.6
通讯作者:
Zhang Lei
Zhang Lei
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Wang Chao;Zhang Wenxiang;Yin Meng-Xin;Hu Lianxin;Li Peixue;Xu Jiajun;Huang Hongling;Wang Shimin;Lu Yi;Wu Wenqing;Ho Margaret S;Li Lin;Zhao Yun;Zhang Lei

文献摘要

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Pez functions as an upstream negative regulator of Yorkie (Yki) to regulate intestinal stem cell (ISC) proliferation and is essential for the activity of the Hippo pathway specifically in theDrosophilamidgut epithelium. Here we report that Suppressor of Deltex (Su(dx)) acts as a negative regulator of Pez. We show that Su(dx) targets Pez for degradation bothin vitroandin vivo. Overexpression of Su(dx) induces proliferation in the fly midgut epithelium, which can be rescued by overexpressed Pez. We also demonstrate that the interaction between Su(dx) and Pez, bridged by WW domains and PY/PPxY motifs, is required for Su(dx)-mediated Pez degradation. Furthermore, we find that Kibra, a binding partner of Pez, stabilizes Pez via WW–PY/PPxY interaction. Moreover, PTPN14, a Pez mammalian homolog, is degraded by overexpressed Su(dx) or Su(dx) homologue WWP1 in mammalian cells. These results reveal a previously unrecognized mechanism of Pez degradation in maintaining the homeostasis ofDrosophilamidgut.