ZSWIM4 regulates embryonic patterning and BMP signaling by promoting nuclear Smad1 degradation

Chengdong Wang; Ziran Liu; Yelin Zeng; Liangji Zhou; Qi Long; Imtiaz Ul Hassan; Yuanliang Zhang; Xufeng Qi; Dongqing Cai; Bingyu Mao; Gang Lu; Jianmin Sun; Yonggang Yao; Yi Deng; Qian Zhao; Bo Feng; Qin Zhou; Wai Yee Chan; Hui Zhao

doi:10.1038/s44319-023-00046-w

ZSWIM4 regulates embryonic patterning and BMP signaling by promoting nuclear Smad1 degradation

Chengdong Wang, Ziran Liu, Yelin Zeng, Liangji Zhou, Qi Long, Imtiaz Ul Hassan, Yuanliang Zhang, Xufeng Qi, Dongqing Cai, Bingyu Mao, Gang Lu, Jianmin Sun, Yonggang Yao, Yi Deng, Qian Zhao, Bo Feng, Qin Zhou, Wai Yee Chan, Hui Zhao

Research output: Journal article publication › Journal article › Academic research › peer-review

2 Citations (Scopus)

Abstract

The dorsoventral gradient of BMP signaling plays an essential role in embryonic patterning. Zinc Finger SWIM-Type Containing 4 (zswim4) is expressed in the Spemann-Mangold organizer at the onset of Xenopus gastrulation and is then enriched in the developing neuroectoderm at the mid-gastrula stages. Knockdown or knockout of zswim4 causes ventralization. Overexpression of zswim4 decreases, whereas knockdown of zswim4 increases the expression levels of ventrolateral mesoderm marker genes. Mechanistically, ZSWIM4 attenuates the BMP signal by reducing the protein stability of SMAD1 in the nucleus. Stable isotope labeling by amino acids in cell culture (SILAC) identifies Elongin B (ELOB) and Elongin C (ELOC) as the interaction partners of ZSWIM4. Accordingly, ZSWIM4 forms a complex with the Cul2-RING ubiquitin ligase and ELOB and ELOC, promoting the ubiquitination and degradation of SMAD1 in the nucleus. Our study identifies a novel mechanism that restricts BMP signaling in the nucleus.

Original language	English
Pages (from-to)	646-671
Number of pages	26
Journal	EMBO Reports
Volume	25
DOIs	https://doi.org/10.1038/s44319-023-00046-w
Publication status	Published - 13 Feb 2024

Keywords

BMP
Cullin RING Ubiquitin Ligase
Spemann–Mangold Organizer
Xenopus
Zswim4

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Genetics

More information

10.1038/s44319-023-00046-w

http://hdl.handle.net/10397/110605

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title = "ZSWIM4 regulates embryonic patterning and BMP signaling by promoting nuclear Smad1 degradation",

abstract = "The dorsoventral gradient of BMP signaling plays an essential role in embryonic patterning. Zinc Finger SWIM-Type Containing 4 (zswim4) is expressed in the Spemann-Mangold organizer at the onset of Xenopus gastrulation and is then enriched in the developing neuroectoderm at the mid-gastrula stages. Knockdown or knockout of zswim4 causes ventralization. Overexpression of zswim4 decreases, whereas knockdown of zswim4 increases the expression levels of ventrolateral mesoderm marker genes. Mechanistically, ZSWIM4 attenuates the BMP signal by reducing the protein stability of SMAD1 in the nucleus. Stable isotope labeling by amino acids in cell culture (SILAC) identifies Elongin B (ELOB) and Elongin C (ELOC) as the interaction partners of ZSWIM4. Accordingly, ZSWIM4 forms a complex with the Cul2-RING ubiquitin ligase and ELOB and ELOC, promoting the ubiquitination and degradation of SMAD1 in the nucleus. Our study identifies a novel mechanism that restricts BMP signaling in the nucleus.",

keywords = "BMP, Cullin RING Ubiquitin Ligase, Spemann–Mangold Organizer, Xenopus, Zswim4",

author = "Chengdong Wang and Ziran Liu and Yelin Zeng and Liangji Zhou and Qi Long and Hassan, {Imtiaz Ul} and Yuanliang Zhang and Xufeng Qi and Dongqing Cai and Bingyu Mao and Gang Lu and Jianmin Sun and Yonggang Yao and Yi Deng and Qian Zhao and Bo Feng and Qin Zhou and Chan, {Wai Yee} and Hui Zhao",

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T1 - ZSWIM4 regulates embryonic patterning and BMP signaling by promoting nuclear Smad1 degradation

AU - Wang, Chengdong

AU - Liu, Ziran

AU - Zeng, Yelin

AU - Zhou, Liangji

AU - Long, Qi

AU - Hassan, Imtiaz Ul

AU - Zhang, Yuanliang

AU - Qi, Xufeng

AU - Cai, Dongqing

AU - Mao, Bingyu

AU - Lu, Gang

AU - Sun, Jianmin

AU - Yao, Yonggang

AU - Deng, Yi

AU - Zhao, Qian

AU - Feng, Bo

AU - Zhou, Qin

AU - Chan, Wai Yee

AU - Zhao, Hui

PY - 2024/2/13

Y1 - 2024/2/13

N2 - The dorsoventral gradient of BMP signaling plays an essential role in embryonic patterning. Zinc Finger SWIM-Type Containing 4 (zswim4) is expressed in the Spemann-Mangold organizer at the onset of Xenopus gastrulation and is then enriched in the developing neuroectoderm at the mid-gastrula stages. Knockdown or knockout of zswim4 causes ventralization. Overexpression of zswim4 decreases, whereas knockdown of zswim4 increases the expression levels of ventrolateral mesoderm marker genes. Mechanistically, ZSWIM4 attenuates the BMP signal by reducing the protein stability of SMAD1 in the nucleus. Stable isotope labeling by amino acids in cell culture (SILAC) identifies Elongin B (ELOB) and Elongin C (ELOC) as the interaction partners of ZSWIM4. Accordingly, ZSWIM4 forms a complex with the Cul2-RING ubiquitin ligase and ELOB and ELOC, promoting the ubiquitination and degradation of SMAD1 in the nucleus. Our study identifies a novel mechanism that restricts BMP signaling in the nucleus.

AB - The dorsoventral gradient of BMP signaling plays an essential role in embryonic patterning. Zinc Finger SWIM-Type Containing 4 (zswim4) is expressed in the Spemann-Mangold organizer at the onset of Xenopus gastrulation and is then enriched in the developing neuroectoderm at the mid-gastrula stages. Knockdown or knockout of zswim4 causes ventralization. Overexpression of zswim4 decreases, whereas knockdown of zswim4 increases the expression levels of ventrolateral mesoderm marker genes. Mechanistically, ZSWIM4 attenuates the BMP signal by reducing the protein stability of SMAD1 in the nucleus. Stable isotope labeling by amino acids in cell culture (SILAC) identifies Elongin B (ELOB) and Elongin C (ELOC) as the interaction partners of ZSWIM4. Accordingly, ZSWIM4 forms a complex with the Cul2-RING ubiquitin ligase and ELOB and ELOC, promoting the ubiquitination and degradation of SMAD1 in the nucleus. Our study identifies a novel mechanism that restricts BMP signaling in the nucleus.

KW - BMP

KW - Cullin RING Ubiquitin Ligase

KW - Spemann–Mangold Organizer

KW - Xenopus

KW - Zswim4

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U2 - 10.1038/s44319-023-00046-w

DO - 10.1038/s44319-023-00046-w

M3 - Journal article

C2 - 38177922

AN - SCOPUS:85185197699

SN - 1469-221X

VL - 25

SP - 646

EP - 671

JO - EMBO Reports

JF - EMBO Reports

ER -

ZSWIM4 regulates embryonic patterning and BMP signaling by promoting nuclear Smad1 degradation

Abstract

Keywords

ASJC Scopus subject areas

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