JMJD6 regulates histone H2A.X phosphorylation and promotes autophagy in triple-negative breast cancer cells via a novel tyrosine kinase activity
JMJD6 regulates histone H2A.X phosphorylation and promotes autophagy in triple-negative breast cancer cells via a novel tyrosine kinase activity
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JMJD6 通过新型酪氨酸激酶活性调节组蛋白 H2A.X 磷酸化并促进三阴性乳腺癌细胞自噬
DOI：
10.1038/s41388-018-0466-y
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发表时间：
2019-02-14
期刊：
影响因子：
8
通讯作者：
Zhang, Xiao-Jun
中科院分区：
文献类型：
--
作者：
Liu, Yan;Long, Yue-Hong;Zhang, Xiao-Jun
Jumonji结构域6(JMJD6)的过度表达已被报道与更具侵袭性的乳腺癌特征有关。然而，JMJD6在乳腺癌发生中的确切作用仍不清楚。在这里，我们证明了JMJD6具有内在的酪氨酸激酶活性，并可以利用ATP和GTP作为磷酸供体来磷酸化组蛋白H_2A.X(H_2A.XY_(39)ph)的Y39。高水平的JMJD6通过调节自噬相关基因的表达促进了三阴性乳腺癌(TNBC)细胞的自噬。JMJD6-H2A.XY39ph轴通过自噬途径促进TNBC细胞生长。我们发现，联合抑制JMJD6激酶活性和自噬有效地降低了TNBC的生长。总之，这些发现建议了一种有效的TNBC治疗策略。
Overexpression of Jumonji domain-containing 6 (JMJD6) has been reported to be associated with more aggressive breast cancer characteristics. However, the precise role of JMJD6 in breast cancer development remains unclear. Here, we demonstrate that JMJD6 has intrinsic tyrosine kinase activity and can utilize ATP and GTP as phosphate donors to phosphorylate Y39 of histone H2A.X (H2A.XY39ph). High JMJD6 levels promoted autophagy in triple negative breast cancer (TNBC) cells by regulating the expression of autophagy-related genes. The JMJD6-H2A.XY39ph axis promoted TNBC cell growth via the autophagy pathway. We show that combined inhibition of JMJD6 kinase activity and autophagy efficiently decreases TNBC growth. Together, these findings suggest an effective strategy for TNBC treatment.