SUMOylation of the Forkhead transcription factor FOXL2 promotes its stabilization/activation through transient recruitment to PML bodies.
SUMOylation of the Forkhead transcription factor FOXL2 promotes its stabilization/activation through transient recruitment to PML bodies.
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DOI：
10.1371/journal.pone.0025463
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Veitia RA
中科院分区：
文献类型：
--
作者：
Georges A;Benayoun BA;Marongiu M;Dipietromaria A;L'Hôte D;Todeschini AL;Auer J;Crisponi L;Veitia RA
FOXL 2是卵巢发育和维持所必需的转录因子。它是突变的遗传条件下称为睑裂狭小，上睑下垂，上睑外翻综合征（BPES）和孤立的卵巢早衰的情况下。我们和其他人以前已经表明，FOXL 2经历了几个翻译后修饰。在这里，使用培养中的细胞，我们表明干扰FOXL 2 SUMO化导致其反式激活能力的强烈抑制，这与稳定性降低相关。有趣的是，FOXL 2 SUMO化促进其瞬时募集到亚核结构中，我们证明该亚核结构是PML（早幼粒细胞白血病）核小体。由于PML小体是核因子翻译后修饰发生的位点，我们使用串联质谱法鉴定FOXL 2的新翻译后修饰。具体而言，我们检测到四个磷酸化，硫酸化和三个乙酰化位点。通过与其他转录因子的类比，我们提出PML核小体可能会短暂地将FOXL 2募集到可能参与FOXL 2翻译后成熟的局部浓缩酶附近。FOXL 2乙酰化、硫酸化、磷酸化以及其他尚未发现的修饰可能会改变FOXL 2的反式激活能力和/或其稳定性，从而调节其整体细胞内活性。
FOXL2 is a transcription factor essential for ovarian development and maintenance. It is mutated in the genetic condition called Blepharophimosis Ptosis Epicantus inversus Syndrome (BPES) and in cases of isolated premature ovarian failure. We and others have previously shown that FOXL2 undergoes several post-translational modifications. Here, using cells in culture, we show that interference with FOXL2 SUMOylation leads to a robust inhibition of its transactivation ability, which correlates with a decreased stability. Interestingly, FOXL2 SUMOylation promotes its transient recruitment to subnuclear structures that we demonstrate to be PML (Promyelocytic Leukemia) Nuclear Bodies. Since PML bodies are known to be sites where post-translational modifications of nuclear factors take place, we used tandem mass spectrometry to identify new post-translational modifications of FOXL2. Specifically, we detected four phosphorylated, one sulfated and three acetylated sites. By analogy with other transcription factors, we propose that PML Nuclear Bodies might transiently recruit FOXL2 to the vicinity of locally concentrated enzymes that could be involved in the post-translational maturation of FOXL2. FOXL2 acetylation, sulfation, phosphorylation as well as other modifications yet to be discovered might alter the transactivation capacity of FOXL2 and/or its stability, thus modulating its global intracellular activity.