FOXO factors: a matter of life and death.
FOXO factors: a matter of life and death.
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DOI：
10.2217/14796694.2.1.83
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发表时间：
2006-02-01
期刊：
影响因子：
--
通讯作者：
Tindall, Donald J
中科院分区：
文献类型：
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作者：
Huang, Haojie;Tindall, Donald J
叉头框O类（FOXO）转录因子，包括FOXO1、FOXO3a和FOXO4，通过抑制细胞增殖、促进细胞凋亡以及保护细胞免受DNA损伤和氧化应激，起到肿瘤抑制蛋白的作用。这些功能的效力受到磷酸化、乙酰化和泛素化的严格调控。新出现的证据表明，FOXO1的蛋白水平受到Akt介导的磷酸化和Skp2介导的泛素化的双重调控。鉴于Akt和Skp2蛋白由于磷酸酶和张力蛋白同源物（PTEN）的缺失在人类癌症中高度活化，FOXO1蛋白的失调似乎是未来药物研发和癌症治疗的一个有前景的靶点。
Forkhead box O-class (FOXO) transcription factors, including FOXO1, FOXO3a and FOXO4, function as tumor-suppressor proteins by inhibiting cell proliferation, promoting apoptotic cell death and protecting cells from DNA damage and oxidative stress. The potency of these functions is regulated tightly by phosphorylation, acetylation and ubiquitination. Emerging evidence indicates that protein levels of FOXO1 are under dual regulation by Ak-mediated phosphorylation and Skp2-mediated ubiquitination. Given that Akt and Skp2 proteins are highly activated in human cancers due to the loss of phosphatase and tensin homolog (PTEN), deregulation of the FOXO1 protein appears to be a promising target for future drug discovery and cancer therapy.