Human ZCCHC12 activates AP-1 and CREB signaling as a transcriptional co-activator
Human ZCCHC12 activates AP-1 and CREB signaling as a transcriptional co-activator
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DOI：
10.1093/abbs/gmp042
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发表时间：
2009-07-01
影响因子：
3.7
通讯作者：
Zhang, Jian
中科院分区：
文献类型：
--
作者：
Li, Hong;Liu, Qian;Zhang, Jian
小鼠锌指CCHC结构域12基因（ZCCHC 12）是骨形态发生蛋白（BMP）信号传导的转录共激活因子，而人ZCCHC 12与非综合征型X连锁智力低下（NS-XLMR）有关。然而，人ZCCHC 12如何参与NS-XLMR的细节仍然不清楚。在这项研究中，我们确定了一个新的核定位信号（NLS）在中间的人ZCCHC 12蛋白，这是负责核定位。多组织北方印迹分析表明ZCCHC 12在人脑中高度表达。此外，原位杂交表明，ZCCHC 12特异性表达于小鼠E10.5胚胎的前脑，中脑和间脑区域的神经上皮细胞。荧光素酶报告基因分析表明，ZCCHC 12作为共激活因子增强了激活蛋白1（AP-1）和cAMP反应元件结合蛋白（CREB）的转录活性。总之，我们在ZCCHC 12中鉴定了一个新的NLS，并发现ZCCHC 12作为AP-1和CREB的转录共激活因子发挥作用。
Mouse zinc finger CCHC domain containing 12 gene (ZCCHC12) has been identified as a transcriptional co-activator of bone morphogenetic protein (BMP) signaling, and human ZCCHC12 was reported to be related to non-syndromic X-linked mental retardation (NS-XLMR). However, the details of how human ZCCHC12 involve in the NS-XLMR still remain unclear. In this study, we identified a novel nuclear localization signal (NLS) in the middle of human ZCCHC12 protein which is responsible for the nuclear localization. Multiple-tissue northern blot analysis indicated that ZCCHC12 is highly expressed in human brain. Furthermore, in situ hybridization showed that ZCCHC12 is specifically expressed in neuroepithelium of forebrain, midbrain, and diencephalon regions of mouse E10.5 embryos. Luciferase reporter assays demonstrated that ZCCHC12 enhanced the transcriptional activities of activator protein 1 (AP-1) and cAMP response element binding protein (CREB) as a coactivator. In conclusion, we identified a new NLS in ZCCHC12 and figured out that ZCCHC12 functions as a transcriptional co-activator of AP-1 and CREB.