Work

The E3 ubiquitin ligase SPRYD3-MYCBP2(PAM) regulates mitotic cell fate and ubiquitination of USP11 to control spindle assembly

Year: 2025

Type: article

Abstract: MYCBP2 (PAM) is a large signaling hub that plays a key role in various processes, including neuronal connectivity and growth, cell division, and protein ubiquitination. Together with the substrate specificity factor FBXO45, MYCBP2 forms an E3 ligase complex that is involved in mitotic cell fate decision. During extended mitotic arrest caused by anti-microtubule drugs, cells may either experience cell death or escape mitosis through mitotic slippage. E3 ligase mediated ubiquitination is antagonized by deubiquitinating enzymes (DUBs). In this study, we show that despite their opposing activities, DUB-E3 ligase complexes can form and cooperate. We identify an E3 ligase complex consisting of MYCBP2 and a new substrate specificity factor, SPRYD3. Interestingly, SPRYD3-MYCBP2 promotes bipolar spindle formation by facilitating non-canonical ubiquitination on the DUB USP11 cysteine 318. We find that this process promotes bipolar spindle formation and mitotic slippage in presence of microtubule targeting drugs.

Source: Journal of Biological Chemistry

DOI: 10.1016/j.jbc.2025.110785

Authors: Alexandra Rita Turi da Fonte Dias, Ingrid Hoffmann

Institution: Heidelberg University

Language: English

Topic: Microtubule and mitosis dynamics

Subfield: Cell Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: gold

Estimated APC paid: $3,430

Funders: Deutsches Krebsforschungszentrum, Imperial College London, Universität Heidelberg, José Carreras Leukämie-Stiftung