ZC4H2 stabilizes Smads to enhance BMP signalling, which is involved in neural development in Xenopus
Ma, Pengcheng1; Ren, Biyu1,2; Yang, Xiangcai1,3,5; Sun, Bin3,4; Liu, Xiaoliang1,3; Kong, Qinghua1,6; Li, Chaocui1; Mao, Bingyu1
2017-08-01
发表期刊OPEN BIOLOGY
ISSN2046-2441
卷号7期号:8页码:170122
摘要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.
关键词Zc4h2 Smad Smurf Bone Morphogenesis Protein Signalling Neural Development
收录类别SCI
语种英语
引用统计
文献类型期刊论文
条目标识符http://ir.kib.ac.cn/handle/151853/54933
专题植物化学与西部植物资源持续利用国家重点实验室
作者单位1.Chinese Acad Sci, Kunming Inst Zool, State Key Lab Genet Resources & Evolut, Kunming 650223, Yunnan, Peoples R China
2.Anhui Univ, Inst Hlth Sci, Hefei 230601, Anhui, Peoples R China
3.Univ Chinese Acad Sci, Kunming Coll Life Sci, Kunming 650203, Yunnan, Peoples R China
4.Chinese Acad Sci & Yunnan Prov, Kunming Inst Zool, Key Lab Anim Models & Human Dis Mech, Kunming 650223, Yunnan, Peoples R China
5.Kunming Univ Sci & Technol, Med Sch, Affiliated Hosp KMUST, Dept Clin Lab, Kunming 650032, Yunnan, Peoples R China
6.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650201, Yunnan, Peoples R China
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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):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),170122.
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):170122.
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