GADD45 family proteins suppress JNK signaling by targeting MKK7.
GADD45 family proteins suppress JNK signaling by targeting MKK7.
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GADD45 家族蛋白通过靶向 MKK7 抑制 JNK 信号传导。
DOI：
10.1016/j.abb.2017.10.005
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发表时间：
2017
影响因子：
3.9
通讯作者：
Sakurai H.
中科院分区：
文献类型：
--
作者：
Ueda T;Kohama Y;Kuge A;Kido E;Sakurai H.
生长停滞和DNA损伤诱导45（GADD 45）家族基因编码相关蛋白，包括GADD 45 α、GADD 45 β和GADD 45 γ。在HeLa细胞中，GADD 45成员的表达在各种环境条件下受到差异调节，但热应激和遗传毒性应激诱导所有基因的表达。GADD 45 β的热休克反应由热休克转录因子1（HSF 1）介导，GADD 45 β是热应激生存所必需的。热和遗传毒性应激诱导的c-Jun N-末端激酶（JNK）的活化受到GADD 45蛋白表达的抑制。GADD 45蛋白结合JNK激酶促分裂原活化蛋白激酶激酶7（MKK 7）并抑制其活性，即使在正常生理条件下也是如此。我们的研究结果表明，GADD 45基本上抑制MKK 7-JNK通路，并表明差异表达的GADD 45家族成员微调应激诱导的JNK活性。
Growth arrest and DNA damage-inducible 45 (GADD45) family genes encode related proteins, including GADD45α, GADD45β, and GADD45γ. In HeLa cells, expression of GADD45 members is differentially regulated under a variety of environmental conditions, but thermal and genotoxic stresses induce the expression of all genes. The heat shock response of GADD45β is mediated by the heat shock transcription factor 1 (HSF1), and GADD45β is necessary for heat stress survival. Heat and genotoxic stress-induced activation of c-Jun N-terminal kinase (JNK) is suppressed by the expression of GADD45 proteins. GADD45 proteins bind the JNK kinase mitogen-activated protein kinase kinase 7 (MKK7) and inhibit its activity, even under normal physiological conditions. Our findings indicate that GADD45 essentially suppresses the MKK7-JNK pathway and suggest that differentially expressed GADD45 family members fine-tune stress-inducible JNK activity.