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EKLF/KLF1在体内被泛素化,其稳定性通过26S蛋白酶体由激活域序列调控。

EKLF/KLF1 is ubiquitinated in vivo and its stability is regulated by activation domain sequences through the 26S proteasome.

作者信息

Quadrini Karen J, Bieker James J

机构信息

The Brookdale Department of Molecular, Cell and Developmental Biology, Mount Sinai School of Medicine, New York, NY 10029, USA.

出版信息

FEBS Lett. 2006 Apr 17;580(9):2285-93. doi: 10.1016/j.febslet.2006.03.039. Epub 2006 Mar 24.

DOI:10.1016/j.febslet.2006.03.039
PMID:16579989
Abstract

Erythroid Krüppel-like factor (EKLF/KLF1) is an erythroid specific, C(2)H(2) zinc finger transcription factor that is essential for the proper chromatin structure and expression of the adult beta-globin gene. Herein, we determine that 26S proteasome inhibitors lead to an accumulation of EKLF protein in murine erythroleukemia (MEL) cells. In addition, EKLF half-life in both MEL cells (<3h) and fetal liver cells (between 6 and 9h) is stabilized in the presence of these inhibitors. EKLF is ubiquitinated in vivo, however its modification does not rely on a particular internal lysine. Finally, EKLF contains two PEST sequences within its N-terminus that have no effect on the ability of EKLF to be ubiquitinated but contribute to its destabilization.

摘要

红系克勒ppel样因子(EKLF/KLF1)是一种红系特异性的C(2)H(2)锌指转录因子,对成人β-珠蛋白基因的正确染色质结构和表达至关重要。在此,我们确定26S蛋白酶体抑制剂导致EKLF蛋白在小鼠红白血病(MEL)细胞中积累。此外,在这些抑制剂存在的情况下,MEL细胞(<3小时)和胎肝细胞(6至9小时)中的EKLF半衰期均得到稳定。EKLF在体内被泛素化,但其修饰并不依赖于特定的内部赖氨酸。最后,EKLF在其N端含有两个PEST序列,这些序列对EKLF被泛素化的能力没有影响,但有助于其不稳定。

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