JTV1 co-activates FBP to induce USP29 transcription and stabilize p53 in response to oxidative stress
JTV1 co-activates FBP to induce USP29 transcription and stabilize p53 in response to oxidative stress
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DOI：
10.1038/emboj.2011.11
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发表时间：
2011-03-02
期刊：
影响因子：
11.4
通讯作者：
Levens, David
中科院分区：
文献类型：
--
作者：
Liu, Juhong;Chung, Hye-Jung;Levens, David
C-myc和p53网络控制增殖、分化和凋亡，并对各种应激、代谢和生物合成过程作出反应和交叉调节。在c-myc上，远上游元件结合蛋白（FBP）和FBP相互作用抑制因子（FIR）通过环接在启动子处的RNA聚合酶II复合物进行转录。另一个FBP伙伴JTV1/AIMP2，一个多氨基酰基- trna合成酶（ARS）复合物的结构亚基，也被报道通过一个明显独立的机制稳定p53。在这里，我们发现在氧化应激的反应中，JTV1从ARS复合体解离，易位到细胞核，与FBP结合并共同激活FBP新靶点泛素特异性肽酶29 （USP29）的转录。USP29是一种以前未被发现的去泛素化酶，它与p53结合，切割多泛素链，并稳定p53。积累的p53迅速诱导细胞凋亡。因此，FBP和JTV1有助于协调分子和细胞对氧化应激的反应。EMBO杂志（2011）30,846-858。doi: 10.1038 / emboj.2011.11;2011年2月1日在线发布
c-myc and p53 networks control proliferation, differentiation, and apoptosis and are responsive to, and cross-regulate a variety of stresses and metabolic and biosynthetic processes. At c-myc, the far upstream element binding protein (FBP) and FBP-interacting repressor (FIR) program transcription by looping to RNA polymerase II complexes engaged at the promoter. Another FBP partner, JTV1/AIMP2, a structural subunit of a multi-aminoacyl-tRNA synthetase (ARS) complex, has also been reported to stabilize p53 via an apparently independent mechanism. Here, we show that in response to oxidative stress, JTV1 dissociates from the ARS complex, translocates to the nucleus, associates with FBP and co-activates the transcription of a new FBP target, ubiquitin-specific peptidase 29 (USP29). A previously uncharacterized deubiquitinating enzyme, USP29 binds to, cleaves poly-ubiquitin chains from, and stabilizes p53. The accumulated p53 quickly induces apoptosis. Thus, FBP and JTV1 help to coordinate the molecular and cellular response to oxidative stress. The EMBO Journal (2011) 30, 846-858. doi: 10.1038/emboj.2011.11; Published online 1 February 2011