Akt is negatively regulated by the MULAN E3 ligase

被引：87

作者：

Bae, Seunghee ^{[1
]}

Kim, Sun-Yong

Jung, Jin Hyuk ^{[1
]}

Yoon, Yeongmin ^{[1
,2
]}

Cha, Hwa Jun ^{[1
]}

Lee, Hyunjin ^{[1
,2
]}

Kim, Karam ^{[1
]}

Kim, Jongran ^{[1
]}

An, In-Sook ^{[1
]}

Kim, Jongdoo ^{[3
]}

Um, Hong-Duck ^{[3
]}

Park, In-Chul ^{[4
]}

Lee, Su-Jae ^{[5
]}

Nam, Seon Young ^{[6
]}

Jin, Young-Woo

Lee, Jae Ho ^{[7
,8
]}

An, Sungkwan ^{[1
,2
]}

机构：

[1] Konkuk Univ, Funct Genoproteome Res Ctr, Seoul 143701, South Korea

[2] Konkuk Univ, LIFEnGENE Inc, Seoul 143701, South Korea

[3] Korea Inst Radiol & Med Sci, Lab Radiat Tumor Physiol, Seoul 139706, South Korea

[4] Korea Inst Radiol & Med Sci, Lab Funct Genom, Seoul 139706, South Korea

[5] Hanyang Univ, Dept Chem, Seoul 133791, South Korea

[6] Radiat Hlth Res Inst KHNP, Div Radiat Effect Res, Seoul 132703, South Korea

[7] Kwandong Univ, Cheil Gen Hosp, Mol Oncol Lab, Seoul 100380, South Korea

[8] Kwandong Univ, Womens Healthcare Ctr, Coll Med, Seoul 100380, South Korea

来源：

CELL RESEARCH | 2012年 / 22卷 / 05期

关键词：

ubiquitin E3 ligase; inhibition; growth regulation; PROTEIN-KINASE-B; GLYCOGEN-SYNTHASE KINASE-3; SIGNAL-TRANSDUCTION; MITOCHONDRIAL E3; BETA-CATENIN; ACTIVATION; PATHWAY; DEGRADATION; INHIBITION; INSULIN;

D O I：

10.1038/cr.2012.38

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：873 / 885

页数：13

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