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Citations to this article

Impaired plasma membrane localization of ubiquitin ligase complex underlies 3-M syndrome development
Pu Wang, … , Scott E. Parnell, Yue Xiong
Pu Wang, … , Scott E. Parnell, Yue Xiong
Published July 25, 2019
Citation Information: J Clin Invest. 2019;129(10):4393-4407. https://doi.org/10.1172/JCI129107.
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Research Article Development Genetics Article has an altmetric score of 4

Impaired plasma membrane localization of ubiquitin ligase complex underlies 3-M syndrome development

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Abstract

3-M primordial dwarfism is an inherited disease characterized by severe pre- and postnatal growth retardation and by mutually exclusive mutations in 3 genes, CUL7, OBSL1, and CCDC8. The mechanism underlying 3-M dwarfism is not clear. We showed here that CCDC8, derived from a retrotransposon Gag protein in placental mammals, exclusively localized on the plasma membrane and was phosphorylated by CK2 and GSK3. Phosphorylation of CCDC8 resulted in its binding first with OBSL1, and then CUL7, leading to the membrane assembly of the 3-M E3 ubiquitin ligase complex. We identified LL5β, a plasma membrane protein that regulates cell migration, as a substrate of 3-M ligase. Wnt inhibition of CCDC8 phosphorylation or patient-derived mutations in 3-M genes disrupted membrane localization of the 3-M complex and accumulated LL5β. Deletion of Ccdc8 in mice impaired trophoblast migration and placental development, resulting in intrauterine growth restriction and perinatal lethality. These results identified a mechanism regulating cell migration and placental development that underlies the development of 3-M dwarfism.

Authors

Pu Wang, Feng Yan, Zhijun Li, Yanbao Yu, Scott E. Parnell, Yue Xiong

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Total citations by year

Year: 2024 2023 2022 2021 2020 Total
Citations: 2 5 4 1 4 16
Citation information
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Citations to this article in year 2022 (4)

Title and authors Publication Year
Ubiquitin ligases: guardians of mammalian development
D Walma, Z Chen, A Bullock, K Yamada
Nature Reviews Molecular Cell Biology 2022
Structure of CRL7FBXW8 reveals coupling with CUL1-RBX1/ROC1 for multi-cullin-RING E3-catalyzed ubiquitin ligation.
Hopf LVM, Baek K, Klügel M, von Gronau S, Xiong Y, Schulman BA
Nature Structural & Molecular Biology 2022
Origination of LTR Retroelement–Derived NYNRIN Coincides with Therian Placental Emergence
Plianchaisuk A, Kusama K, Kato K, Sriswasdi S, Tamura K, Iwasaki W
Molecular Biology and Evolution 2022
Never-homozygous genetic variants in healthy populations are potential recessive disease candidates.
Schmenger T, Diwan GD, Singh G, Apic G, Russell RB
npj Genomic Medicine 2022

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