Modification of Drosophila p53 by SUMO modulates its transactivation and pro-apoptotic functions.
Conjugation to SUMO is a reversible post-translational modification that regulates several transcription factors involved in cell proliferation, differentiation, and disease. The p53 tumor suppressor can be modified by SUMO-1 in mammalian cells, but the functional consequences of this modification are unclear. Here, we demonstrate that the Drosophila homolog of human p53 can be efficiently sumoylated in insect cells. We identify two lysine residues involved in SUMO attachment, one at the C terminus, between the DNA binding and oligomerization domains, and one at the N terminus of the protein. We find that sumoylation helps recruit Drosophila p53 to nuclear dot-like structures that can be marked by human PML and the Drosophila homologue of Daxx. We demonstrate that mutation of both sumoylation sites dramatically reduces the transcriptional activity of p53 and its ability to induce apoptosis in transgenic flies, providing in vivo evidence that sumoylation is critical for Drosophila p53 function.
Mauri
Federico
F
Laboratorio Nazionale Consorzio Interuniversitario Biotecnologie, AREA Science Park, Padriciano 99, Trieste, Italy.
McNamee
Laura M
LM
Lunardi
Andrea
A
Chiacchiera
Fulvio
F
Del Sal
Giannino
G
Brodsky
Michael H
MH
Collavin
Licio
L
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis; D002454:Cell Differentiation; D049109:Cell Proliferation; D004330:Drosophila / Q000378:metabolism*; D008954:Models, Biological; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism*; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; C526347:Daxx protein, Drosophila; D009687:Nuclear Proteins; D012333:RNA, Messenger; D025841:Small Ubiquitin-Related Modifier Proteins; D016159:Tumor Suppressor Protein p53