Please use this identifier to cite or link to this item: https://doi.org/10.1111/j.1349-7006.2009.01180.x
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dc.titleCytoplasmic tethering is involved in synergistic inhibition of p53 by Mdmx and Mdm2
dc.contributor.authorOhtsubo, C.
dc.contributor.authorShiokawa, D.
dc.contributor.authorKodama, M.
dc.contributor.authorGaiddon, C.
dc.contributor.authorNakagama, H.
dc.contributor.authorJochemsen, A.G.
dc.contributor.authorTaya, Y.
dc.contributor.authorOkamoto, K.
dc.date.accessioned2016-11-08T08:25:52Z
dc.date.available2016-11-08T08:25:52Z
dc.date.issued2009
dc.identifier.citationOhtsubo, C., Shiokawa, D., Kodama, M., Gaiddon, C., Nakagama, H., Jochemsen, A.G., Taya, Y., Okamoto, K. (2009). Cytoplasmic tethering is involved in synergistic inhibition of p53 by Mdmx and Mdm2. Cancer Science 100 (7) : 1291-1299. ScholarBank@NUS Repository. https://doi.org/10.1111/j.1349-7006.2009.01180.x
dc.identifier.issn13479032
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/129733
dc.description.abstractThe mdm2 and mdmx oncogenes play essential yet nonredundant roles in synergistic inactivatiosn of p53. However, the biochemical mechanism by which Mdmx synergizes with Mdm2 to inhibit p53 function remains obscure. Here we demonstrate that, using nonphosphorylatable mutants of Mdmx, the cooperative inhibition of p53 by Mdmx and Mdm2 was associated with cytoplasmic localization of p53, and with an increase of the interaction of Mdmx to p53 and Mdm2 in the cytoplasm. In addition, the Mdmx mutant cooperates with Mdm2 to induce ubiquitination of p53 at C-terminal lysine residues, and the integrity of the C-terminal lysines was partly required for the cooperative inhibition. The expression of subcellular localization mutants of Mdmx revealed that subcellular localization of Mdmx dictated p53 localization, and that cytoplasmic Mdmx tethered p53 in the cytoplasm and efficiently inhibited p53 activity. RNAi-mediated inhibition of Mdmx or introduction of the nuclear localization mutant of Mdmx reduced cytoplasmic retention of p53 in neuroblastoma cells, in which cytoplasmic sequestration of p53 is involved in its inactivation. Our data indicate that cytoplasmic tethering of p53 mediated by Mdmx contributes to p53 inactivation in some types of cancer cells. © 2009 Japanese Cancer Association.
dc.description.urihttp://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1111/j.1349-7006.2009.01180.x
dc.sourceScopus
dc.typeArticle
dc.contributor.departmentCANCER SCIENCE INSTITUTE OF SINGAPORE
dc.contributor.departmentBIOCHEMISTRY
dc.description.doi10.1111/j.1349-7006.2009.01180.x
dc.description.sourcetitleCancer Science
dc.description.volume100
dc.description.issue7
dc.description.page1291-1299
dc.description.codenCSACC
dc.identifier.isiut000266982000021
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