RNF12 controls embryonic stem cell fate and morphogenesis in zebrafish embryos by targeting Smad7 for degradation

Molecular Cell
Long ZhangPeter ten Dijke

Abstract

TGF-β members are of key importance during embryogenesis and tissue homeostasis. Smad7 is a potent antagonist of TGF-β family/Smad-mediated responses, but the regulation of Smad7 activity is not well understood. We identified the RING domain-containing E3 ligase RNF12 as a critical component of TGF-β signaling. Depletion of RNF12 dramatically reduced TGF-β/Smad-induced effects in mammalian cells, whereas ectopic expression of RNF12 strongly enhanced these responses. RNF12 specifically binds to Smad7 and induces its polyubiquitination and degradation. Smad7 levels were increased in RNF12-deficient mouse embryonic stem cells, resulting in mitigation of both BMP-mediated repression of neural induction and activin-induced anterior mesoderm formation. RNF12 also antagonized Smad7 during Nodal-dependent and BMP-dependent signaling and morphogenic events in early zebrafish embryos. The gastrulation defects induced by ectopic and depleted Smad7 were rescued in part by RNF12 gain and loss of function, respectively. These findings demonstrate that RNF12 plays a critical role in TGF-β family signaling.

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Citations

Apr 24, 2014·Protein & Cell·Juan ZhangFangfang Zhou
Sep 25, 2014·Science China. Life Sciences·FangFang ZhouLong Zhang
Mar 5, 2015·European Journal of Human Genetics : EJHG·Elin TønneTorunn Fiskerstrand
Jan 30, 2016·European Journal of Clinical Investigation·Gianluigi GiannelliAranzazu Sanchez
Feb 2, 2017·Proceedings of the National Academy of Sciences of the United States of America·Smitha SripathyAntonio Bedalov
Dec 7, 2016·Cold Spring Harbor Perspectives in Biology·Keiji Miyazawa, Kohei Miyazono
Dec 1, 2017·Acta Biochimica Et Biophysica Sinica·Feng XieLong Zhang
Sep 7, 2017·Proceedings of the National Academy of Sciences of the United States of America·Yi YuXin-Hua Feng
Dec 14, 2017·Nature Communications·Zhengkui ZhangLong Zhang
Nov 3, 2016·Development·Yangsook Song GreenJan L Christian
Nov 11, 2018·The Journal of Biological Chemistry·Fang WangYide Mei
Jun 18, 2017·Cell Death and Differentiation·Long ZhangFangfang Zhou
Jun 4, 2019·International Journal of Molecular Sciences·Dian WangWeiwei Zhang
Dec 12, 2017·Acta Biochimica Et Biophysica Sinica·Xiaohua YanYe-Guang Chen
Mar 22, 2014·EMBO Reports·Alexandros StrikoudisIannis Aifantis
Nov 19, 2019·Frontiers in Cell and Developmental Biology·Feng Wang, Ingolf Bach
Dec 18, 2020·Cell Death and Differentiation·Jun-O JinPeter Chang-Whan Lee
Jan 10, 2021·International Journal of Molecular Sciences·Abhishek SinhaPeter Ten Dijke
Aug 6, 2019·Current Opinion in Cell Biology·Yi Yu, Xin-Hua Feng
Apr 9, 2021·Proceedings of the National Academy of Sciences of the United States of America·Benjamin TajerMary C Mullins
May 6, 2021·International Journal of Molecular Sciences·Tanuza DasEunice EunKyeong Kim
Jun 2, 2021·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Yiping HuQingwen Wang

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