Siddiqa A, Sims-Mourtada J C, Guzman-Rojas L, Rangel R, Guret C, Madrid-Marina V, Sun Y, Martinez-Valdez H
Department of Immunology, Box 178, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA.
Nature. 2001 Mar 15;410(6826):383-7. doi: 10.1038/35066602.
Proteins containing AT hooks bind A/T-rich DNA through a nine-amino-acid motif and are thought to co-regulate transcription by modifying the architecture of DNA, thereby enhancing the accessibility of promoters to transcription factors. Here we describe AKNA, a human AT-hook protein that directly binds the A/T-rich regulatory elements of the promoters of CD40 and CD40 ligand (CD40L) and coordinately regulates their expression. Consistent with its function, AKNA is a nuclear protein that contains multiple PEST protein-cleavage motifs, which are common in regulatory proteins with high turnover rates. AKNA is mainly expressed by B and T lymphocytes, natural killer cells and dendritic cells. During B-lymphocyte differentiation, AKNA is mainly expressed by germinal centre B lymphocytes, a stage in which receptor and ligand interactions are crucial for B-lymphocyte maturation. Our findings show that an AT-hook molecule can coordinately regulate the expression of a key receptor and its ligand, and point towards a molecular mechanism that explains homotypic cell interactions.
含有AT钩的蛋白质通过一个九氨基酸基序与富含A/T的DNA结合，并且被认为通过改变DNA结构来共同调节转录，从而增强启动子对转录因子的可及性。在此，我们描述了AKNA，一种人类AT钩蛋白，它直接结合CD40和CD40配体（CD40L）启动子的富含A/T的调控元件，并协同调节它们的表达。与其功能一致，AKNA是一种核蛋白，含有多个PEST蛋白切割基序，这些基序在周转率高的调控蛋白中很常见。AKNA主要由B淋巴细胞、T淋巴细胞、自然杀伤细胞和树突状细胞表达。在B淋巴细胞分化过程中，AKNA主要由生发中心B淋巴细胞表达，在这个阶段受体和配体相互作用对B淋巴细胞成熟至关重要。我们的研究结果表明，一个AT钩分子可以协同调节关键受体及其配体的表达，并指向一种解释同型细胞相互作用的分子机制。
