Functional analysis and intracellular localization of p53 modified by SUMO-1.
p53 tumor suppressor is a subject of several post-translational modifications, including phosphorylation, ubiquitination and acetylation, which regulate p53 function. A new covalent modification of p53 at lysine 386 by SUMO-1 was recently identified. To elucidate the function of sumoylated p53, we compared the properties of wild type p53 and sumoylation-deficient p53 mutant, K386R. No differences were found between wild type p53 and K386R mutant of p53 in transactivation or growth suppression assays. Moreover, overexpression of SUMO-1 has no effect on p53-regulated transcription. Biochemical fractionation showed that sumoylated p53 is localized in the nucleus and is tightly bound to chromatin structures. p53 and SUMO-1 co-localized in PML nuclear bodies in 293 cells and the nucleoli in MCF7 and HT1080 cells. However, sumoylation-deficient p53 mutant showed a similar pattern of intranuclear localization, suggesting that SUMO-1 does not target p53 to subnuclear structures. These data indicate that SUMO-1 modification of p53 at lysine 386 may not be essential for p53's cellular localization, transcriptional activation, or growth regulation.
Kwek
S S
SS
Department of Molecular Genetics, College of Medicine, University of Illinois at Chicago, 900 South Ashland Avenue, Chicago, Illinois, IL 60607, USA.
Derry
J
J
Tyner
A L
AL
Shen
Z
Z
Gudkov
A V
AV
D000595:Amino Acid Sequence; D002455:Cell Division / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D004249:DNA Damage; D006801:Humans; D025842:SUMO-1 Protein; D017386:Sequence Homology, Amino Acid; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014452:Ubiquitins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*
D002843:Chromatin; D025842:SUMO-1 Protein; D016159:Tumor Suppressor Protein p53; D014452:Ubiquitins