Dovat Sinisa, Ronni Tapani, Russell Dana, Ferrini Roger, Cobb Bradley S, Smale Stephen T
Howard Hughes Medical Institute, Department of Microbiology, Immunology, and Molecular Genetics, California 90095, USA.
Genes Dev. 2002 Dec 1;16(23):2985-90. doi: 10.1101/gad.1040502.
Many nuclear proteins are inactivated during mitotic entry, presumably as a prerequisite to chromatin condensation and cell division. C2H2 zinc fingers define the largest transcription factor family in the human proteome. The linker separating finger motifs is highly conserved and resembles TGEKP in more than 5000 occurrences. However, the reason for this conservation is not fully understood. We demonstrate that all three linkers in the DNA-binding domain of Ikaros are phosphorylated during mitosis. Phosphomimetic substitutions abolished DNA-binding and pericentromeric localization. A linker within Sp1 was also phosphorylated, suggesting that linker phosphorylation provides a global mechanism for inactivation of the C2H2 family.
许多核蛋白在进入有丝分裂期间会失活，这大概是染色质浓缩和细胞分裂的一个先决条件。C2H2锌指结构定义了人类蛋白质组中最大的转录因子家族。分隔指基序的连接区高度保守，在超过5000次出现中类似于TGEKP。然而，这种保守性的原因尚未完全了解。我们证明，Ikaros的DNA结合结构域中的所有三个连接区在有丝分裂期间都会被磷酸化。模拟磷酸化的替代物消除了DNA结合和着丝粒周围定位。Sp1中的一个连接区也被磷酸化，这表明连接区磷酸化提供了一种使C2H2家族失活的全局机制。
