Kang Kyoung Ah, Piao Mei Jing, Ryu Yea Seong, Maeng Young Hee, Hyun Jin Won
School of Medicine, Jeju National University, Jeju, Republic of Korea.
J Cell Physiol. 2017 Jul;232(7):1914-1921. doi: 10.1002/jcp.25746. Epub 2017 Feb 21.
Runt domain transcription factor 3 (RUNX3) is a transcription factor that functions as a tumor suppressor. RUNX3 is frequently inactivated by epigenetic silencing or its protein mislocalization (cytoplasmic localization) in many cancer types. This study investigated whether oxidative stress induces redistribution of RUNX3 from the nucleus to the cytoplasm. The cytoplasmic localization of RUNX3 was associated with oxidative stress-induced RUNX3 phosphorylation at tyrosine residues via SRC activation. Moreover, oxidative stress increased expression of histone deacetylases (HDACs). RUNX3 phosphorylation and SRC expression induced by oxidative stress were inhibited by knockdown of HDAC1, restoring the nuclear localization of RUNX3 under oxidative stress. In conclusion, these results demonstrate that HDAC1- and SRC-mediated phosphorylation of RUNX3 induced by oxidative stress is associated with the cytoplasmic localization of RUNX3 and can lead to RUNX3 inactivation and carcinogenesis. J. Cell. Physiol. 232: 1914-1921, 2017. © 2016 Wiley Periodicals, Inc.
runt结构域转录因子3（RUNX3）是一种发挥肿瘤抑制作用的转录因子。在许多癌症类型中，RUNX3经常因表观遗传沉默或其蛋白质错误定位（细胞质定位）而失活。本研究调查了氧化应激是否会诱导RUNX3从细胞核重新分布到细胞质。RUNX3的细胞质定位与通过SRC激活导致的氧化应激诱导的RUNX3酪氨酸残基磷酸化有关。此外，氧化应激增加了组蛋白去乙酰化酶（HDACs）的表达。通过敲低HDAC1可抑制氧化应激诱导的RUNX3磷酸化和SRC表达，从而在氧化应激下恢复RUNX3的核定位。总之，这些结果表明，氧化应激诱导的HDAC1和SRC介导的RUNX3磷酸化与RUNX3的细胞质定位有关，并可能导致RUNX3失活和致癌作用。《细胞生理学杂志》232: 1914 - 1921, 2017。© 2016威利期刊公司。
