ASB2 is a novel E3 ligase of SMAD9 required for cardiogenesis

Abstract Cardiogenesis requires the orchestrated spatiotemporal tuning of BMP signalling upon the balance between induction and counter-acting suppression of the differentiation of the cardiac tissue. SMADs are key intracellular transducers and the selective degradation of SMADs by the ubiquitin–pro...

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Autores principales:	Kyung-Duk Min, Masanori Asakura, Manabu Shirai, Satoru Yamazaki, Shin Ito, Hai Ying Fu, Hiroshi Asanuma, Yoshihiro Asano, Tetsuo Minamino, Seiji Takashima, Masafumi Kitakaze
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2198c64f663f4df99340febaa636532e
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spelling	oai:doaj.org-article:2198c64f663f4df99340febaa636532e2021-12-05T12:15:52ZASB2 is a novel E3 ligase of SMAD9 required for cardiogenesis10.1038/s41598-021-02390-02045-2322https://doaj.org/article/2198c64f663f4df99340febaa636532e2021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-02390-0https://doaj.org/toc/2045-2322Abstract Cardiogenesis requires the orchestrated spatiotemporal tuning of BMP signalling upon the balance between induction and counter-acting suppression of the differentiation of the cardiac tissue. SMADs are key intracellular transducers and the selective degradation of SMADs by the ubiquitin–proteasome system is pivotal in the spatiotemporal tuning of BMP signalling. However, among three SMADs for BMP signalling, SMAD1/5/9, only the specific E3 ligase of SMAD9 remains poorly investigated. Here, we report for the first time that SMAD9, but not the other SMADs, is ubiquitylated by the E3 ligase ASB2 and targeted for proteasomal degradation. ASB2, as well as Smad9, is conserved among vertebrates. ASB2 expression was specific to the cardiac region from the very early stage of cardiac differentiation in embryogenesis of mouse. Knockdown of Asb2 in zebrafish resulted in a thinned ventricular wall and dilated ventricle, which were rescued by simultaneous knockdown of Smad9. Abundant Smad9 protein leads to dysregulated cardiac differentiation through a mechanism involving Tbx2, and the BMP signal conducted by Smad9 was downregulated under quantitative suppression of Smad9 by Asb2. Our findings demonstrate that ASB2 is the E3 ligase of SMAD9 and plays a pivotal role in cardiogenesis through regulating BMP signalling.Kyung-Duk MinMasanori AsakuraManabu ShiraiSatoru YamazakiShin ItoHai Ying FuHiroshi AsanumaYoshihiro AsanoTetsuo MinaminoSeiji TakashimaMasafumi KitakazeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Kyung-Duk Min Masanori Asakura Manabu Shirai Satoru Yamazaki Shin Ito Hai Ying Fu Hiroshi Asanuma Yoshihiro Asano Tetsuo Minamino Seiji Takashima Masafumi Kitakaze ASB2 is a novel E3 ligase of SMAD9 required for cardiogenesis
description	Abstract Cardiogenesis requires the orchestrated spatiotemporal tuning of BMP signalling upon the balance between induction and counter-acting suppression of the differentiation of the cardiac tissue. SMADs are key intracellular transducers and the selective degradation of SMADs by the ubiquitin–proteasome system is pivotal in the spatiotemporal tuning of BMP signalling. However, among three SMADs for BMP signalling, SMAD1/5/9, only the specific E3 ligase of SMAD9 remains poorly investigated. Here, we report for the first time that SMAD9, but not the other SMADs, is ubiquitylated by the E3 ligase ASB2 and targeted for proteasomal degradation. ASB2, as well as Smad9, is conserved among vertebrates. ASB2 expression was specific to the cardiac region from the very early stage of cardiac differentiation in embryogenesis of mouse. Knockdown of Asb2 in zebrafish resulted in a thinned ventricular wall and dilated ventricle, which were rescued by simultaneous knockdown of Smad9. Abundant Smad9 protein leads to dysregulated cardiac differentiation through a mechanism involving Tbx2, and the BMP signal conducted by Smad9 was downregulated under quantitative suppression of Smad9 by Asb2. Our findings demonstrate that ASB2 is the E3 ligase of SMAD9 and plays a pivotal role in cardiogenesis through regulating BMP signalling.
format	article
author	Kyung-Duk Min Masanori Asakura Manabu Shirai Satoru Yamazaki Shin Ito Hai Ying Fu Hiroshi Asanuma Yoshihiro Asano Tetsuo Minamino Seiji Takashima Masafumi Kitakaze
author_facet	Kyung-Duk Min Masanori Asakura Manabu Shirai Satoru Yamazaki Shin Ito Hai Ying Fu Hiroshi Asanuma Yoshihiro Asano Tetsuo Minamino Seiji Takashima Masafumi Kitakaze
author_sort	Kyung-Duk Min
title	ASB2 is a novel E3 ligase of SMAD9 required for cardiogenesis
title_short	ASB2 is a novel E3 ligase of SMAD9 required for cardiogenesis
title_full	ASB2 is a novel E3 ligase of SMAD9 required for cardiogenesis
title_fullStr	ASB2 is a novel E3 ligase of SMAD9 required for cardiogenesis
title_full_unstemmed	ASB2 is a novel E3 ligase of SMAD9 required for cardiogenesis
title_sort	asb2 is a novel e3 ligase of smad9 required for cardiogenesis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/2198c64f663f4df99340febaa636532e
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ASB2 is a novel E3 ligase of SMAD9 required for cardiogenesis

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