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Acta Biochimica et Biophysica Sinica Advance Access originally published online on May 29, 2009
Acta Biochimica et Biophysica Sinica 2009 41(7):535-544; doi:10.1093/abbs/gmp042
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© The Author 2009. Published by ABBS Editorial Office in association with Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.

Human ZCCHC12 activates AP-1 and CREB signaling as a transcriptional co-activator

Hong Li{dagger}, Qian Liu{dagger}, Xiang Hu{dagger}, Du Feng, Shuanglin Xiang, Zhicheng He, Xingwang Hu, Jianlin Zhou, Xiaofeng Ding, Chang Zhou and Jian Zhang*

Key Laboratory of Protein Chemistry and Developmental Biology of State Education Ministry of China, College of Life Science, Hunan Normal University, Changsha 410081, China

* Correspondence author. Tel/Fax: +86-731-8872792; E-mail: zhangjian{at}hunnu.edu.cn


  Abstract

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 co-activator. 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.

Keywords    zinc finger protein; ZCCHC12; AP-1; CREB

Received: February 13, 2009; Accepted: March 27, 2009

{dagger} These authors contributed equally to this work.


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