IKBKE phosphorylation and inhibition of FOXO3a: a mechanism of IKBKE oncogenic function.
IKBKE phosphorylation and inhibition of FOXO3a: a mechanism of IKBKE oncogenic function.
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DOI：
10.1371/journal.pone.0063636
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Cheng JQ
中科院分区：
文献类型：
--
作者：
Guo JP;Tian W;Shu S;Xin Y;Shou C;Cheng JQ
叉头盒O （FOXO）转录因子是细胞存活和生长的关键调控因子。FOXO的转录活性和亚细胞定位受到翻译后修饰的严格调控。这里我们报道IKBKE通过磷酸化FOXO3a- ser644调控FOXO3a。FOXO3a的磷酸化导致其降解和核细胞质易位。先前的研究表明IKBKE直接激活Akt， Akt通过磷酸化Ser32、Ser253和Ser315抑制FOXO3a。然而，akt -非磷酸化FOXO3a-A3的活性（即将3个丝氨酸残基转化为丙氨酸）被IKBKE抑制。此外，IKBKE的过表达与原发性肺和乳腺肿瘤中pFOXO3a-S644水平升高相关。IKBKE抑制FOXO3a和FOXO3a- a3的细胞功能，但对FOXO3a- s644a的抑制程度要小得多。这些发现表明IKBKE主要通过SerS644的磷酸化调控FOXO3a，并且IKBKE至少在一定程度上通过调控FOXO3a发挥其细胞功能。
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.
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影响因子：
64.5
作者：
Brunet, A;Bonni, A;Greenberg, ME
通讯作者：
Greenberg, ME
DOI：
10.1083/jcb.200307056
发表时间：
2004-01-19
期刊：
The Journal of cell biology
影响因子：
--
作者：
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通讯作者：
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影响因子：
5.4
作者：
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通讯作者：
Udalova, Irina A.
影响因子：
6
作者：
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通讯作者：
Cheng, Jin Q.
影响因子：
16
作者：
Comb, William C.;Hutti, Jessica E.;Baldwin, Albert S.
通讯作者：
Baldwin, Albert S.