Akt is negatively regulated by the MULAN E3 ligase
Akt is negatively regulated by the MULAN E3 ligase
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DOI：
10.1038/cr.2012.38
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发表时间：
2012-05-01
期刊：
影响因子：
44.1
通讯作者：
An, Sungkwan
中科院分区：
文献类型：
--
作者：
Bae, Seunghee;Kim, Sun-Yong;An, Sungkwan
丝氨酸/苏氨酸激酶Akt在多种细胞过程中发挥作用，包括细胞存活和肿瘤发生。对Akt负性调节机制的研究主要集中在去磷酸化介导的失活。在这项研究中，我们发现了Akt的负调控因子木兰，它同时具有环指结构域和E3泛素连接酶活性。AKT直接与花木兰相互作用，并在体内外被花木兰泛素化。其他分子分析表明，磷酸化Akt是与花木兰相互作用和泛素化的实质性靶点。功能研究结果表明，木兰对Akt的降解抑制了细胞的增殖和活力。这些数据提供了对Akt泛素化信号网络的洞察。
The serine/threonine kinase Akt functions in multiple cellular processes, including cell survival and tumor development. Studies of the mechanisms that negatively regulate Akt have focused on dephosphorylation-mediated inactivation. In this study, we identified a negative regulator of Akt, MULAN, which possesses both a RING finger domain and E3 ubiquitin ligase activity. Akt was found to directly interact with MULAN and to be ubiquitinated by MULAN in vitro and in vivo. Other molecular assays demonstrated that phosphorylated Akt is a substantive target for both interaction with MULAN and ubiquitination by MULAN. The results of the functional studies suggest that the degradation of Akt by MULAN suppresses cell proliferation and viability. These data provide insight into the Akt ubiquitination signaling network.