WDR79 mediates the proliferation of non-small cell lung cancer cells by regulating the stability of UHRF1.
WDR79 mediates the proliferation of non-small cell lung cancer cells by regulating the stability of UHRF1.
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WDR79通过调节UHRF1稳定性介导非小细胞肺癌细胞增殖
DOI：
10.1111/jcmm.13580
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发表时间：
2018-05
影响因子：
5.3
通讯作者：
Ye M
中科院分区：
文献类型：
--
作者：
Chen J;Sheng X;Ma H;Tang Z;Yang C;Cao L;Sun Y;Deng T;Feng P;Hu B;Wei D;Liu J;Xiong W;Ye M
WD重复序列蛋白79（WD repeat protein 79，WDR 79）是WD重复序列蛋白家族的成员，其特征在于存在一系列WD重复序列结构域，并且是参与端粒酶组装、Cajal体形成和DNA双链断裂修复的支架蛋白。尽管先前的研究表明，WDR 79在非小细胞肺癌（NSCLC）中经常过表达，并促进NSCLC细胞的增殖，但WDR 79介导的NSCLC增殖的潜在机制尚未完全了解。在这项研究中，我们报告了一种新的分子功能的WDR 79介导的NSCLC细胞增殖，通过控制UHRF 1的稳定性。在细胞核中，WDR 79与UHRF 1共定位并相互作用。结果，WDR 79的过表达稳定了UHRF 1，而WDR 79的切除降低了UHRF 1的水平。同时，我们发现WDR 79可以保护UHRF 1免受多聚泛素化介导的蛋白水解，这有助于UHRF 1的稳定。我们进一步证明了WDR 79通过稳定UHRF 1对NSCLC细胞发挥增殖作用。这些结果表明，WDR 79是一种新的UHRF 1调节剂，通过维持UHRF 1的稳定性，他们也提供了一个线索，如何探索WDR 79在NSCLC的潜在治疗应用。
WD repeat protein 79 (WDR79) is a member of the WD‐repeat protein family characterized by the presence of a series of WD‐repeat domains and is a scaffold protein that participates in telomerase assembly, Cajal body formation and DNA double strand break repair. Although previous studies have revealed that WDR79 is frequently overexpressed in non‐small cell lung cancer (NSCLC) and promotes the proliferation of NSCLC cells, the underlying mechanism responsible for WDR79‐mediated NSCLC proliferation is not fully understood. In this study, we report a novel molecular function of WDR79 that mediates NSCLC cell proliferation by controlling the stability of UHRF1. In the nucleus, WDR79 colocalized and interacted with UHRF1. As a result, overexpression of WDR79 stabilized UHRF1, whereas ablation of WDR79 decreased the level of UHRF1. Meanwhile, we showed that WDR79 can protect UHRF1 from poly‐ubiquitination‐mediated proteolysis, which facilitated the stabilization of UHRF1. We further demonstrated that WDR79 exerts a proliferation effect on NSCLC cells by stabilizing UHRF1. These findings reveal that WDR79 is a novel UHRF1 regulator by maintaining UHRF1 stability, and they also provide a clue as to how to explore WDR79 for potential therapeutic application in NSCLC.
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影响因子：
64.8
作者：
Batista, Luis F. Z.;Pech, MatthewF.;Zhong, Franklin L.;Nguyen, Ha Nam;Xie, Kathleen T.;Zaug, Arthur J.;Crary, Sharon M.;Choi, Jinkuk;Sebastiano, Vittorio;Cherry, Athena;Giri, Neelam;Wernig, Marius;Alter, Blanche P.;Cech, Thomas R.;Savage, Sharon A.;Pera, Renee A. Reijo;Artandi, Steven E.
通讯作者：
Artandi, Steven E.
影响因子：
44.1
作者：
Qin W;Wolf P;Liu N;Link S;Smets M;La Mastra F;Forné I;Pichler G;Hörl D;Fellinger K;Spada F;Bonapace IM;Imhof A;Harz H;Leonhardt H
通讯作者：
Leonhardt H
影响因子：
10.5
作者：
Henriksson S;Rassoolzadeh H;Hedström E;Coucoravas C;Julner A;Goldstein M;Imreh G;Zhivotovsky B;Kastan MB;Helleday T;Farnebo M
通讯作者：
Farnebo M
TCAB1：头颈癌诊断和治疗的潜在靶点
影响因子：
37.3
作者：
Sun CK;Luo XB;Gou YP;Hu L;Wang K;Li C;Xiang ZT;Zhang P;Kong XL;Zhang CL;Yang Q;Li J;Xiao LY;Li Y;Chen QM
通讯作者：
Chen QM
WDR79 通过 USP7 介导的 Mdm2-p53 通路调节促进非小细胞肺癌细胞增殖
影响因子：
9
作者：
Sun Y;Cao L;Sheng X;Chen J;Zhou Y;Yang C;Deng T;Ma H;Feng P;Liu J;Tan W;Ye M
通讯作者：
Ye M