DUSP13B/TMDP inhibits stress-activated MAPKs and suppresses AP-1-dependent gene expression

DUSP13B/TMDP inhibits stress-activated MAPKs and suppresses AP-1-dependent gene expression
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DOI:
10.1007/s11010-011-0749-x
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发表时间:
2011-06-01
影响因子:
4.3
通讯作者:
Shima, Hiroshi
Shima, Hiroshi
中科院分区:
生物学3区
文献类型:
--
作者:
Katagiri, Chiaki;Masuda, Kouhei;Shima, Hiroshi

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双特异性磷酸酶(DUSP)13基因使用替代外显子编码两种非典型DUSP,DUSP 13 B/TMDP和DUSP 13 A/MDSP。DUSP 13 B蛋白在睾丸中表达最高,特别是在精母细胞和曲细精管的圆形精子细胞中,而DUSP 13 A蛋白仅限于骨骼肌。在这里,我们显示DUSP 13 B在细胞中以选择性JNK = p38 > ERK的顺序灭活MAPK活化,而DUSP 13 A不显示MAPK磷酸酶活性。报告基因分析表明,DUSP 13 B对AP-1依赖性基因的表达有明显的抑制作用,而DUSP 13 A则无此作用。据我们所知,DUSP 13 B是第一个鉴定的睾丸特异性磷酸酶,抑制应激激活的MAPK。这些数据表明DUSP 13 B在精子发生期间保护免受外部应激的重要作用。
The dual-specificity phosphatase (DUSP) 13 gene encodes two atypical DUSPs, DUSP13B/TMDP and DUSP13A/MDSP using alternative exons. DUSP13B protein is most highly expressed in testis, particularly in spermatocytes and round spermatids of the seminiferous tubules, while that of DUSP13A is restricted to skeletal muscle. Here, we show that DUSP13B inactivated MAPK activation in the order of selectivity, JNK = p38 > ERK in cells, while DUSP13A did not show MAPK phosphatase activity. Reporter gene analysis showed that DUSP13B had significant inhibitory effect on AP-1-dependent gene expression, but DUSP13A did not. To our knowledge, DUSP13B is the first identified testis-specific phosphatase that inhibits stress-activated MAPKs. These data suggest an important role for DUSP13B in protection from external stress during spermatogenesis.