机构：[1]State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, People’s Republic of China[2]Institute of Health Sciences, Anhui University, Hefei 230601, People’s Republic of China[3]Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming 650203, People’s Republic of China[4]Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming 650223, People’s Republic of China[5]Department of Clinical Laboratory, The Affiliated Hospital of KMUST, Medical School, Kunming University of Science and Technology, Kunming 650032, People’s Republic of China.[6]State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, People’s Republic of China.
Bone morphogenetic proteins (BMPs) play vital roles in regulating stem cell maintenance, differentiation and embryonic development. Intracellularly, BMP signalling is mediated by Smad proteins, which are regulated post-transcriptionally through reversible phosphorylation and ubiquitination. ZC4H2 is a small nuclear protein associated with intellectual disability and neural development in humans. Here, we report that ZC4H2 is highly expressed in the developing neural system and is involved in neural patterning and BMP signalling in Xenopus. Knockdown of ZC4H2 led to expansion of the expression of the pan neural plate marker Sox2 in Xenopus embryos. In mammalian cells, ZC4H2 promotes BMP signalling and is involved in BMP regulated myogenic and osteogenic differentiation of mouse myoblast cells. Mechanistically, ZC4H2 binds and stabilizes Smad1 and Smad5 proteins through reducing their association with the Smurf ubiquitin ligases and thus their ubiquitination. We also found that a group of ZC4H2 mutations, which have been isolated in patients with intellectual disorders, showed weaker Smad-stabilizing activity, suggesting that the ZC4H2-Smad interaction might contribute to proper neural development in humans.
基金：
The West Light
Foundation of The Chinese Academy of Sciences, NSFC-Yunnan
Joint Funds (U1302226) and Yunnan Applied Basic Research Project
(No. 2016FB043).
第一作者机构：[1]State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, People’s Republic of China
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Ma Pengcheng,Ren Biyu,Yang Xiangcai,et al.ZC4H2 stabilizes Smads to enhance BMP signalling, which is involved in neural development in Xenopus[J].OPEN BIOLOGY.2017,7(8):doi:10.1098/rsob.170122.
APA：
Ma, Pengcheng,Ren, Biyu,Yang, Xiangcai,Sun, Bin,Liu, Xiaoliang...&Mao, Bingyu.(2017).ZC4H2 stabilizes Smads to enhance BMP signalling, which is involved in neural development in Xenopus.OPEN BIOLOGY,7,(8)
MLA：
Ma, Pengcheng,et al."ZC4H2 stabilizes Smads to enhance BMP signalling, which is involved in neural development in Xenopus".OPEN BIOLOGY 7..8(2017)
