Characterization of nuclear localization and SUMOylation of the ATBF1 transcription factor in epithelial cells.

Characterization of nuclear localization and SUMOylation of the ATBF1 transcription factor in epithelial cells.
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DOI:
10.1371/journal.pone.0092746
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Dong JT
Dong JT
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Sun X;Li J;Dong FN;Dong JT

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ATBF 1/ZFHX 3是一个大的转录因子,在发育,肿瘤发生和其他生物学过程中发挥作用。ATBF 1通常定位于细胞核中,但在癌细胞中经常错误定位于细胞质中。ATBF 1错误定位的潜在机制尚不清楚。在这项研究中,我们分析了ATBF 1的核定位,发现异位表达的ATBF 1在细胞核中形成核体(NB)样点,其中一些确实与早幼粒细胞白血病(PML)NB物理相关。我们还定义了一个3-氨基酸基序,KRK 2615 -2617,作为ATBF 1的核定位信号(NLS)。有趣的是,弥散分布的核SUMO 1蛋白被隔离成ATBF 1点,这可能与ATBF 1与PML NB(已知的SUMO化热点)的物理关联有关。此外,ATBF 1本身是SUMO化的。ATBF 1 SUMO化发生在3个以上的赖氨酸残基,包括K2349、K2806和K3258,并且具有核特异性。最后,与ATBF 1直接相互作用的PIAS 3 SUMO 1 E3连接酶减少而不是增强ATBF 1 SUMO化,阻止ATBF 1与SUMO 1在细胞核中的共定位。这些结果表明,核定位和SUMO化是重要的转录因子功能的ATBF 1,ATBF 1可以协同PML NB调节蛋白SUMO化在不同的生物过程。
ATBF1/ZFHX3 is a large transcription factor that functions in development, tumorigenesis and other biological processes. ATBF1 is normally localized in the nucleus, but is often mislocalized in the cytoplasm in cancer cells. The mechanism underlying the mislocalization of ATBF1 is unknown. In this study, we analyzed the nuclear localization of ATBF1, and found that ectopically expressed ATBF1 formed nuclear body (NB)-like dots in the nucleus, some of which indeed physically associated with promyelocytic leukemia (PML) NBs. We also defined a 3-amino acid motif, KRK2615-2617, as the nuclear localization signal (NLS) for ATBF1. Interestingly, diffusely distributed nuclear SUMO1 proteins were sequestered into ATBF1 dots, which could be related to ATBF1's physical association with PML NBs, known SUMOylation hotspots. Furthermore, ATBF1 itself was SUMOylated. ATBF1 SUMOylation occurred at more than 3 lysine residues including K2349, K2806 and K3258 and was nuclear specific. Finally, the PIAS3 SUMO1 E3 ligase, which interacts with ATBF1 directly, diminished rather than enhanced ATBF1 SUMOylation, preventing the co-localization of ATBF1 with SUMO1 in the nucleus. These findings suggest that nuclear localization and SUMOylation are important for the transcription factor function of ATBF1, and that ATBF1 could cooperate with PML NBs to regulate protein SUMOylation in different biological processes.
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