Section of Virology, Imperial College Faculty of Medicine, Norfolk Place, London W2 1PG, UK.
Nucleic Acids Res. 2013 Feb 1;41(3):1555-68. doi: 10.1093/nar/gks1273. Epub 2012 Dec 18.
RUNX family proteins are expressed from alternate promoters, giving rise to different N-terminal forms, but the functional difference of these isoforms is not understood. Here, we show that growth of a human B lymphoblastoid cell line infected with Epstein-Barr virus is inhibited by RUNX1c but not by RUNX1b. This gives a novel functional assay for the unique N-terminus of RUNX1c, and amino acids of RUNX1c required for the effect have been identified. Primary resting B cells contain RUNX1c, consistent with the growth inhibitory effect in B cells. The oncogene TEL-RUNX1 lacks the N-terminus of RUNX1c because of the TEL fusion and does not inhibit B cell growth. Mouse Runx1c lacks some of the sequences required for human RUNX1c to inhibit B cell growth, indicating that this aspect of human B cell growth control may differ in mice. Remarkably, a cell-penetrating peptide containing the N-terminal sequence of RUNX1c specifically antagonizes the growth inhibitory effect in B lymphoblastoid cells and might be used to modulate the function of human RUNX1c.
RUNX 家族蛋白通过不同的启动子表达，产生不同的 N 端形式，但这些异构体的功能差异尚不清楚。在这里，我们发现感染 Epstein-Barr 病毒的人类 B 淋巴母细胞系的生长受到 RUNX1c 的抑制，但不受 RUNX1b 的抑制。这为 RUNX1c 的独特 N 端提供了一种新的功能测定方法，并确定了 RUNX1c 发挥作用所需的氨基酸。静止的原代 B 细胞含有 RUNX1c，这与 B 细胞中的生长抑制作用一致。由于 TEL 融合，致癌基因 TEL-RUNX1 缺失了 RUNX1c 的 N 端，并且不能抑制 B 细胞的生长。小鼠 Runx1c 缺失了一些人类 RUNX1c 抑制 B 细胞生长所必需的序列，这表明人类 B 细胞生长调控的这一方面在小鼠中可能不同。值得注意的是，含有 RUNX1c N 端序列的穿透肽特异性拮抗 B 淋巴母细胞系的生长抑制作用，并且可以用于调节人类 RUNX1c 的功能。
