Open AccessNuclear Akt interacts with B23/NPM and protects it from proteolytic cleavage, enhancing cell survival
Author(s) -
Sang Bae Lee,
Truong L.X. Nguyen,
Jongeun Choi,
Kyung-Hoon Lee,
SungWoo Cho,
Zhixue Liu,
Keqiang Ye,
Sun Sik Bae,
Jee-Yin Ahn
Publication year - 2008
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0807668105
Subject(s) - protein kinase b , nucleoplasm , microbiology and biotechnology , pleckstrin homology domain , proto oncogene proteins c akt , sumo protein , biology , akt2 , cell cycle , nuclear protein , chemistry , akt1 , cytoplasm , apoptosis , signal transduction , biochemistry , transcription factor , nucleolus , ubiquitin , gene
B23/NPM is a major nucleolar phosphoprotein that has a critical role in cell proliferation and cell death. Here, we show that it forms a complex with Akt on growth factor (GF) stimulation in both the cytoplasm and the nucleus, for which Akt activation is indispensable. The C terminus of B23 (239–294 residues) potently binds pleckstrin homology (PH) domain of Akt. Akt binding to B23 protects it from proteolytic degradation by caspase-3, leading to the up-regulation of cell survival. Interestingly, unsumoylated B23 K263R, but not wild-type B23, strongly interacts with Akt in the nucleoplasm in the absence of GFs. Furthermore, we show that Akt2, but not other isoforms, specifically regulates B23 sumoylation and protein stability. Also, nuclear Akt regulates the cell cycle progression activity of B23. Therefore, our findings support that nuclear Akt binds and stabilizes B23 in the nucleoplasm, and regulates its activities in cell survival and cell cycle.