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XB-ART-53938
Open Biol. August 1, 2017; 7 (8):

ZC4H2 stabilizes Smads to enhance BMP signalling, which is involved in neural development in Xenopus.

Ma P , Ren B , Yang X , Sun B , Liu X , Kong Q , Li C , Mao B .


Abstract
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.

PubMed ID: 28814648
PMC ID: PMC5577449
Article link: Open Biol.

Genes referenced: myf5 myod1 runx2 smad1 smurf1 smurf2 snai2 sox2 tgfb1 xk81a1 zc4h2

Morpholinos referenced: zc4h2 MO1

References:
Balemans, 2002, Pubmed, Xenbase[+]


Article Images: [+] show captions

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