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dc.contributor.authorZhu, Jidong
dc.contributor.authorBlenis, John
dc.contributor.authorYuan, Junying
dc.date.accessioned2019-10-05T16:04:56Z
dc.date.issued2008
dc.identifier.citationZhu, J., J. Blenis, and J. Yuan. 2008. “Activation of PI3K/Akt and MAPK Pathways Regulates Myc-Mediated Transcription by Phosphorylating and Promoting the Degradation of Mad1.” Proceedings of the National Academy of Sciences 105 (18): 6584–89. https://doi.org/10.1073/pnas.0802785105.
dc.identifier.issn0027-8424
dc.identifier.issn0744-2831
dc.identifier.issn1091-6490
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41483478*
dc.description.abstractMad1, a member of the Myc/Max/Mad family, suppresses Myc-mediated transcriptional activity by competing with Myc for heterodimerization with its obligatory partner, Max. The expression of Mad1 suppresses Myc-mediated cell proliferation and transformation. The levels of Mad1 protein are generally low in many human cancers, and Mad1 protein has a very short half-life. However, the mechanism that regulates the turnover of Mad1 protein is poorly understood. In this study, we showed that Mad1 is a substrate of p90 ribosomal kinase (RSK) and p70 S6 kinase (S6K). Both RSK and S6K phosphorylate serine 145 of Mad1 upon serum or insulin stimulation. Ser-145 phosphorylation of Mad1 accelerates the ubiquitination and degradation of Mad1 through the 26S proteasome pathway, which in turn promotes the transcriptional activity of Myc. Our study provides a direct link between the growth factor signaling pathways regulated by PI3 kinase/Akt and MAP kinases with Myc-mediated transcription.
dc.language.isoen_US
dc.publisherNational Academy of Sciences
dash.licenseLAA
dc.titleActivation of PI3K/Akt and MAPK pathways regulates Myc-mediated transcription by phosphorylating and promoting the degradation of Mad1
dc.typeJournal Article
dc.description.versionVersion of Record
dc.relation.journalProceedings of the National Academy of Sciences of the United States of America
dash.depositing.authorYuan, Junying::c7e832b918fc7c2356d6c49fe1a0b135::600
dc.date.available2019-10-05T16:04:56Z
dash.workflow.comments1Science Serial ID 90170
dc.identifier.doi10.1073/pnas.0802785105
dash.source.volume105;18
dash.source.page6584


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