Show simple item record

dc.contributor.authorWei, Xiaolong
dc.contributor.authorYu, Zhong Kang
dc.contributor.authorRamalingam, Arivudainambi
dc.contributor.authorGrossman, Steven R.
dc.contributor.authorYu, Jiang H.
dc.contributor.authorBloch, Donald B.
dc.contributor.authorMaki, Carl G.
dc.date.accessioned2019-10-17T05:19:01Z
dc.date.issued2003
dc.identifier.citationWei, Xiaolong, Zhong Kang Yu, Arivudainambi Ramalingam, Steven R. Grossman, Jiang H. Yu, Donald B. Bloch, and Carl G. Maki. 2003. “Physical and Functional Interactions between PML and MDM2.” Journal of Biological Chemistry 278 (31). American Society for Biochemistry & Molecular Biology (ASBMB): 29288–97. doi:10.1074/jbc.m212215200.
dc.identifier.issn0021-9258
dc.identifier.issn1083-351X
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41555764*
dc.description.abstractThe tumor suppressor protein PML and oncoprotein MDM2 have opposing effects on p53. PML stimulates p53 activity by recruiting it to nuclear foci termed PML nuclear bodies. In contrast, MDM2 inhibits p53 by promoting its degradation. To date, neither a physical nor functional relationship between PML and MDM2 has been described. In this study, we report an in vivo and in vitro interaction between PML and MDM2 which is independent of p53. Two separate regions of PML are recognized which can interact with MDM2. The C-terminal half of PML, encoded by residues 300 - 633, can interact with the central region of MDM2 which includes the MDM2 acidic domain. In addition, PML amino acids 1 - 200, which encode the RING-finger and most of the B box zinc binding motifs, can interact with the C-terminal, RING-finger containing region of MDM2. Interestingly, PML mutants in which sumoylation at lysine 160 was inhibited displayed an increased association with MDM2, suggesting that sumoylation at this site may be a determinant of PML-MDM2 binding. Coexpression with MDM2 caused a redistribution of PML from the nucleus to the cytoplasm, and this required the PML N terminus and the MDM2 RING-finger domain. These results suggest that interaction between the PML N terminus and MDM2 C terminus can promote PML nuclear exclusion. Wild-type MDM2 inhibited the ability of PML to stimulate the transcriptional activity of a GAL4-CBP fusion protein. This inhibition required the central, acidic region of MDM2, but did not require the MDM2 C terminus. Taken together, these studies demonstrate that MDM2 and PML can interact through at least two separate protein regions, and that these interactions can have specific effects on the activity and/or localization of PML.
dc.language.isoen_US
dc.publisherAmerican Society for Biochemistry and Molecular Biology
dash.licenseLAA
dc.titlePhysical and Functional Interactions between PML and MDM2
dc.typeJournal Article
dc.description.versionVersion of Record
dc.relation.journalThe Journal of Biological Chemistry
dash.depositing.authorBloch, Donald B.::d6e81c79e2b5a07d97c85ebcf0a58059::600
dc.date.available2019-10-17T05:19:01Z
dash.workflow.comments1Science Serial ID 106144
dc.identifier.doi10.1074/jbc.M212215200
dash.source.volume278;31
dash.source.page29288-29297


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record