Identification of domains responsible for ubiquitin-dependent degradation of dMyc by glycogen synthase kinase 3β and casein kinase 1 kinases

Margherita Galletti, Sara Riccardo, Federica Parisi, Carlina Lora, Mahesh Kumar Saqcena, Leinny Rivas, Bonnie Wong, Alexis Serra, Florenci Serras, Daniela Grifoni, PierGiuseppe Pelicci, Jin Jiang, Paola Bellosta

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

In the present study, we report that ubiquitin-mediated degradation of dMyc, the Drosophila homologue of the human c-myc proto-oncogene, is regulated in vitro and in vivo by members of the casein kinase 1 (CK1) family and by glycogen synthase kinase 3β (GSK3β). Using Drosophila S2 cells, we demonstrate that CK1α promotes dMyc ubiquitination and degradation with a mechanism similar to the one mediated by GSK3β in vertebrates. Mutation of ck1α or -ε or sgg/gsk3β in Drosophila wing imaginal discs results in the accumulation of dMyc protein, suggesting a physiological role for these kinases in vivo. Analysis of the dMyc amino acid sequence reveals the presence of conserved domains containing potential phosphorylation sites for mitogen kinases, GSK3β, and members of the CK1 family. We demonstrate that mutations of specific residues within these phosphorylation domains regulate dMyc protein stability and confer resistance to degradation by CK1α and GSK3β kinases. Expression of the dMyc mutants in the compound eye of the adult fly results in a visible defect that is attributed to the effect of dMyc on growth, cell death, and inhibition of ommatidial differentiation.

Original languageEnglish (US)
Pages (from-to)3424-3434
Number of pages11
JournalMolecular and cellular biology
Volume29
Issue number12
DOIs
StatePublished - Jun 2009

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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