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EMBO Rep 2024 Feb 01;252:646-671. doi: 10.1038/s44319-023-00046-w.
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ZSWIM4 regulates embryonic patterning and BMP signaling by promoting nuclear Smad1 degradation.

Wang C , Liu Z , Zeng Y , Zhou L , Long Q , Hassan IU , Zhang Y , Qi X , Cai D , Mao B , Lu G , Sun J , Yao Y , Deng Y , Zhao Q , Feng B , Zhou Q , Chan WY , Zhao H .

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.

PubMed ID: 38177922
PMC ID: PMC10897318
Article link: EMBO Rep
Grant support: [+]

Species referenced: Xenopus tropicalis Xenopus laevis
Genes referenced: babam2 bmp2 bmp4 cer1 chrd cul2 elob eloc fgf8 gsc id2 kctd15 krt12.4 msx1 myc otx2 smad1 smad2 smad4 smurf1 smurf2 sox2 sox3 szl tbxt ventx1.2 ventx2.2 wnt3a zswim4
GO keywords: embryo development [+]
Antibodies: FLAG Ab3 Gadph Ab9 HA Ab10 Myc Ab16 Smad1 Ab12 Smad1 Ab2
Morpholinos: zswim4 MO1 zswim4 MO2 zswim4 MO3 zswim7 MO1
gRNAs referenced: zswim4 gRNA1 zswim4 gRNA2 zswim4 gRNA3 zswim4 gRNA4 zswim4 gRNA5

Article Images: [+] show captions
References [+] :
Agius, Endodermal Nodal-related signals and mesoderm induction in Xenopus. 2000, Pubmed, Xenbase