Smurf1 and Smurf2 Mediated Polyubiquitination and Degradation of RNF220 Suppresses Shh-group Medulloblastoma

Overview

Journal Cell Death Dis

Specialties Cell Biology
General Medicine

Date 2023 Aug 3

PMID 37537194

Authors

Yuwei Li

Huishan Wang

Bin Sun

Guifeng Su

Yu Cang

Ling Zhao

Shuhua Zhao

Yan Li

Bingyu Mao

Pengcheng Ma

Affiliations

Soon will be listed here.

Abstract

Sonic hedgehog (Shh)-group medulloblastoma (MB) (Shh-MB) encompasses a clinically and molecularly distinct group of cancers originating from the developing nervous system with aberrant high Shh signaling as a causative driver. We recently reported that RNF220 is required for sustained high Shh signaling during Shh-MB progression; however, how high RNF220 expression is achieved in Shh-MB is still unclear. In this study, we found that the ubiquitin E3 ligases Smurf1 and Smurf2 interact with RNF220, and target it for polyubiquitination and degradation. In MB cells, knockdown or overexpression of Smurf1 or Smurf2 promotes or inhibits cell proliferation, colony formation and xenograft growth, respectively, by controlling RNF220 protein levels, and thus modulating Shh signaling. Furthermore, in clinical human MB samples, the protein levels of Smurf1 or Smurf2 were negatively correlated with those of RNF220 or GAB1, a Shh-MB marker. Overall, this study highlights the importance of the Smurf1- and Smurf2-RNF220 axes during the pathogenesis of Shh-MB and provides new therapeutic targets for Shh-MB treatment.

Citing Articles

SMURF1 and SMURF2 directly target GLI1 for ubiquitination and proteasome-dependent degradation.

Bordin F, Terriaca G, Apostolico A, Di Fiore A, Mir F, Bellardinelli S Cell Death Discov. 2024; 10(1):498.

PMID: 39695131 PMC: 11655642. DOI: 10.1038/s41420-024-02260-4.

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