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

Wang, Chengdong1; Liu, Ziran2; Zeng, Yelin1; Zhou, Liangji1; Long, Qi1; Ul Hassan, Imtiaz1; Zhang, Yuanliang3; Qi, Xufeng4; Cai, Dongqing4; Mao, Bingyu5,6; Lu, Gang1; Sun, Jianmin7; Yao, Yonggang5,6; Deng, Yi8,9; Zhao, Qian3; Feng, Bo1; Zhou, Qin10; Chan, Wai Yee1,11,12; Zhao, Hui1,11,12

2024-02-13

10.1038/s44319-023-00046-w

EMBO REPORTS   影响因子和分区

1469-221X

1469-3178

["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.","Zswim4 fine-tunes BMP signaling in Xenopus early embryonic patterning by interacting with the Cul2-RING ubiquitin ligase, Elongin B and C, thereby forming a protein disruption complex that ultimately reduces nuclear Smad1 protein stability.Zswim4 is a novel inhibitor of the BMP signaling pathway, localized in the nucleus. Zswim4 physically interacts with Smad1 through the Smad1 MH1 domain. Zswim4 reduces Smad1 stability and increases Smad1 ubiquitination in the nucleus. Zswim4 interacts with Cullin2 and Elongin B and C, forming a protein disruption complex to promote Smad1 ubiquitination.","Zswim4 fine-tunes BMP signaling in Xenopus early embryonic patterning by interacting with the Cul2-RING ubiquitin ligase, Elongin B and C, thereby forming a protein disruption complex that ultimately reduces nuclear Smad1 protein stability."]

Zswim4 BMP Spemann-Mangold Organizer Xenopus Cullin RING Ubiquitin Ligase

SCI

英语

其他

National Key R&D Program of China[2019YFA0904500] ; National Key R&D Program of China, Synthetic Biology Research["14112618","14119120"] ; Research Grants Council of Hong Kong[C5033-19E] ; CRF equipment grant[8601012]

Biochemistry & Molecular Biology ; Cell Biology

Biochemistry & Molecular Biology ; Cell Biology

WOS:001204722700009

SPRINGERNATURE

MOLECULAR BIOLOGY & GENETICS

Web of Science

1.Chinese Univ Hong Kong, Fac Med, Sch Biomed Sci, Key Lab Regenerat Med,Minist Educ, Hong Kong, Peoples R China
2.Qingdao Municipal Ctr Dis Control & Prevent, Qingdao 266033, Shandong, Peoples R China
3.Hong Kong Polytech Univ, Dept Appl Biol & Chem Technol, State Key Lab Chem Biol & Drug Discovery, Hong Kong, Peoples R China
4.Jinan Univ, Dept Dev & Regenerat Biol, Key Lab Regenerat Med, Minist Educ, Guangzhou 510632, Guangdong, Peoples R China
5.Kunming Inst Zool, Chinese Acad Sci, Key Lab Anim Models & Human Dis Mech, Kunming 650223, Yunnan, Peoples R China
6.Kunming Inst Zool Chinese Univ Hong Kong KIZ CUHK, Chinese Acad Sci, Kunming, Peoples R China
7.Ningxia Med Univ, Sch Basic Med Sci, Dept Pathogen Biol & Immunol, 1160 Shengli St, Yinchuan 750004, Peoples R China
8.Southern Univ Sci & Technol, Dept Biol, Guangdong Prov Key Lab Cell Microenvironm & Dis Re, Shenzhen 518055, Peoples R China
9.Southern Univ Sci & Technol, Shenzhen Key Lab Cell Microenvironm, Shenzhen 518055, Peoples R China
10.Harbin Med Univ, Sch Basic Med Sci, Harbin 150081, Peoples R China
11.Chinese Univ Hong Kong KIZ CUHK, Kunming Inst Zool, Hong Kong, Peoples R China
12.Chinese Univ Hong Kong, Hong Kong Branch, CAS Ctr Excellence Anim Evolut & Genet, Hong Kong, Peoples R China

Wang, Chengdong,Liu, Ziran,Zeng, Yelin,et al. ZSWIM4 regulates embryonic patterning and BMP signaling by promoting nuclear Smad1 degradation[J]. EMBO REPORTS,2024,25(2).

Wang, Chengdong.,Liu, Ziran.,Zeng, Yelin.,Zhou, Liangji.,Long, Qi.,...&Zhao, Hui.(2024).ZSWIM4 regulates embryonic patterning and BMP signaling by promoting nuclear Smad1 degradation.EMBO REPORTS,25(2).

Wang, Chengdong,et al."ZSWIM4 regulates embryonic patterning and BMP signaling by promoting nuclear Smad1 degradation".EMBO REPORTS 25.2(2024).