| Title | IKBKE Phosphorylation and Inhibition of FOXO3a: A Mechanism of IKBKE Oncogenic Function |
| Authors | Guo, Jian-Ping Tian, Wei Shu, Shaokun Xin, Yu Shou, Chengchao Cheng, Jin Q. |
| Affiliation | Peking Univ, Canc Hosp & Inst, Dept Biochem & Mol Biol, Beijing 100871, Peoples R China. Univ S Florida, H Lee Moffitt Canc Ctr, Dept Mol Oncol, Tampa, FL 33682 USA. |
| Keywords | FORKHEAD TRANSCRIPTION FACTOR BREAST-CANCER ONCOGENE TUMOR-SUPPRESSOR CYLD KAPPA-B ACTIVATION IKK-EPSILON PROMOTES TUMORIGENESIS OXIDATIVE STRESS EMERGING ROLES EXPRESSION PROTEIN |
| Issue Date | 2013 |
| Publisher | plos one |
| Citation | PLOS ONE.2013,8,(5). |
| Abstract | Forkhead box O (FOXO) transcription factors are emerging as key regulators of cell survival and growth. The transcriptional activity and subcellular localization of FOXO are tightly regulated by post-translational modifications. Here we report that IKBKE regulates FOXO3a through phosphorylation of FOXO3a-Ser644. The phosphorylation of FOXO3a resulted in its degradation and nuclear-cytoplasmic translocation. Previous studies have shown that IKBKE directly activates Akt and that Akt inhibits FOXO3a by phosphorylation of Ser32, Ser253 and Ser315. However, the activity of Akt-nonphosphorytable FOXO3a-A3 (i.e., converting 3 serine residues to alanine) was inhibited by IKBKE. Furthermore, overexpression of IKBKE correlates with elevated levels of pFOXO3a-S644 in primary lung and breast tumors. IKBKE inhibits cellular function of FOXO3a and FOXO3a-A3 but, to a much less extent, of FOXO3a-S644A. These findings suggest that IKBKE regulates FOXO3a primarily through phosphorylation of SerS644 and that IKBKE exerts its cellular function, at least to some extent, through regulation of FOXO3a. |
| URI | http://hdl.handle.net/20.500.11897/190160 |
| ISSN | 1932-6203 |
| DOI | 10.1371/journal.pone.0063636 |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 北京肿瘤医院 |
