Ubiquitylation of the ER-Shaping Protein Lunapark via the CRL3KLHL12 Ubiquitin Ligase Complex
Yuniati, Laurensia; Lauriola, Angela; Gerritsen, Manouk; Abreu, Susana; Ni, Eric; Tesoriero, Chiara; Onireti, Jacob O.; Low, Teck Yew; Heck, Albert J.R.; Vettori, Andrea; Cardozo, Timothy; Guardavaccaro, Daniele
(2020) Cell Reports, volume 31, issue 7, pp. 1 - 20
(Article)
Abstract
Yuniati et al. perform a proteomic screen to identify E3 substrates that are ubiquitylated at cellular membranes and find that the ER-shaping protein Lunapark is ubiquitylated by the CRL3KLHL12 ubiquitin ligase. They show that Lunapark binds mTORC1 and affects its activity, and defects in Lunapark ubiquitylation lead to neurodevelopmental defects.
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Keywords: cullin-RING ligases, endoplasmic reticulum, ER three-way junction, Lunapark, lysosome, mTORC1, ubiquitin, General Biochemistry,Genetics and Molecular Biology
ISSN: 2211-1247
Publisher: Cell Press
Note: Funding Information: The authors thank M. Rossi, C. Rabouille, and M. Perduca for helpful comments and discussion, the aquarium team of the Interdepartmental Centre for Experimental Research (C.I.R.S.A.L.) (University of Verona) for zebrafish husbandry, L. Di Marcotullio for reagents, and L.M. Young, C. Valdes Quezada, Z. Lei, R. Magliozzi, M. Marogna, and E. Cadoria for contributions. This work was funded by grants from the Dutch Cancer Society (KWF) and Fondazione Cariverona to D.G. Funding Information: The authors thank M. Rossi, C. Rabouille, and M. Perduca for helpful comments and discussion, the aquarium team of the Interdepartmental Centre for Experimental Research (C.I.R.S.A.L.) (University of Verona) for zebrafish husbandry, L. Di Marcotullio for reagents, and L.M. Young, C. Valdes Quezada, Z. Lei, R. Magliozzi, M. Marogna, and E. Cadoria for contributions. This work was funded by grants from the Dutch Cancer Society (KWF) and Fondazione Cariverona to D.G. Conceptualization, L.Y. A.L. A.V. T.C. and D.G.; Methodology, L.Y. A.L. M.G. S.A. E.N. C.T. J.O.O. and T.Y.L.; Investigation, L.Y. A.L. M.G. S.A. E.N. C.T. J.O.O. and T.Y.L.; Writing, D.G.; Funding Acquisition, D.G.; Resources, A.V. T.C. A.J.R.H. and D.G.; Supervision, D.G. The authors declare no competing interests. Publisher Copyright: © 2020 The Author(s)
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