Dynamic regulation of Oct1 during mitosis by phosphorylation and ubiquitination.
Dynamic regulation of Oct1 during mitosis by phosphorylation and ubiquitination.
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DOI：
10.1371/journal.pone.0023872
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Tantin D
中科院分区：
文献类型：
--
作者：
Kang J;Goodman B;Zheng Y;Tantin D
转录因子Oct1调控多种细胞过程。众所周知，它在细胞周期和应激过程中被磷酸化，但上游激酶和下游后果尚不清楚。其中一种在S335位点磷酸化的修饰形式缺乏结合DNA的能力。除磷酸化外，其他修饰状态未被描述。我们发现，在m期，Oct1 DNA结合域的S335位点被nima相关激酶Nek6磷酸化。Phospho-Oct1也被泛素化。磷酸化将Oct1排除在有丝分裂染色质之外。相反，Oct1pS335集中在中心体、有丝分裂纺锤杆、着丝点和中间体。Oct1 siRNA敲低会减弱这些位置的信号。Oct1消融和过表达都会导致有丝分裂异常。S335对于过表达表型很重要，暗示该残基参与有丝分裂调节。Oct1缺失导致爪蟾卵提取物纺锤体形态发生缺陷，确立了Oct1有丝分裂特异性功能。Oct1与纤层蛋白B1在纺锤极和体中部共定位。在中体，两种蛋白质相互需要才能正确地定位对方。我们发现磷酸化oct1在有丝分裂后期被非规范的k11连接的多泛素链修饰。泛素化需要后期促进复合体，我们进一步发现后期促进复合体大亚基APC1和Oct1pS335相互作用。这些发现揭示了有丝分裂过程中Oct1磷酸化和去丝化之间的机制耦合，以及Oct1在有丝分裂中的作用。
Transcription factor Oct1 regulates multiple cellular processes. It is known to be phosphorylated during the cell cycle and by stress, however the upstream kinases and downstream consequences are not well understood. One of these modified forms, phosphorylated at S335, lacks the ability to bind DNA. Other modification states besides phosphorylation have not been described. We show that Oct1 is phosphorylated at S335 in the Oct1 DNA binding domain during M-phase by the NIMA-related kinase Nek6. Phospho-Oct1 is also ubiquitinated. Phosphorylation excludes Oct1 from mitotic chromatin. Instead, Oct1pS335 concentrates at centrosomes, mitotic spindle poles, kinetochores and the midbody. Oct1 siRNA knockdown diminishes the signal at these locations. Both Oct1 ablation and overexpression result in abnormal mitoses. S335 is important for the overexpression phenotype, implicating this residue in mitotic regulation. Oct1 depletion causes defects in spindle morphogenesis in Xenopus egg extracts, establishing a mitosis-specific function of Oct1. Oct1 colocalizes with lamin B1 at the spindle poles and midbody. At the midbody, both proteins are mutually required to correctly localize the other. We show that phospho-Oct1 is modified late in mitosis by non-canonical K11-linked polyubiquitin chains. Ubiquitination requires the anaphase-promoting complex, and we further show that the anaphase-promoting complex large subunit APC1 and Oct1pS335 interact. These findings reveal mechanistic coupling between Oct1 phosphorylation and ubquitination during mitotic progression, and a role for Oct1 in mitosis.
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DOI：
10.1083/jcb.200804155
发表时间：
2009-01-12
期刊：
The Journal of cell biology
影响因子：
--
作者：
Malhas AN;Lee CF;Vaux DJ
通讯作者：
Vaux DJ
影响因子：
64.8
作者：
Guelen, Lars;Pagie, Ludo;van Steensel, Bas
通讯作者：
van Steensel, Bas
影响因子：
64.5
作者：
Joukov, Vladimir;Groen, Aaron C.;Livingston, David M.
通讯作者：
Livingston, David M.
影响因子：
64.5
作者：
Maiato, H;Fairley, EAL;Earnshaw, WC
通讯作者：
Earnshaw, WC
网络建模将乳腺癌易感性与中心体功能障碍联系起来
影响因子：
30.8
作者：
Pujana, Miguel Angel;Han, Jing-Dong J.;Vidal, Marc
通讯作者：
Vidal, Marc