dc.contributor.author | Zhu, Jidong | |
dc.contributor.author | Blenis, John | |
dc.contributor.author | Yuan, Junying | |
dc.date.accessioned | 2019-10-05T16:04:56Z | |
dc.date.issued | 2008 | |
dc.identifier.citation | Zhu, 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.issn | 0027-8424 | |
dc.identifier.issn | 0744-2831 | |
dc.identifier.issn | 1091-6490 | |
dc.identifier.uri | http://nrs.harvard.edu/urn-3:HUL.InstRepos:41483478 | * |
dc.description.abstract | Mad1, 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.iso | en_US | |
dc.publisher | National Academy of Sciences | |
dash.license | LAA | |
dc.title | Activation of PI3K/Akt and MAPK pathways regulates Myc-mediated transcription by phosphorylating and promoting the degradation of Mad1 | |
dc.type | Journal Article | |
dc.description.version | Version of Record | |
dc.relation.journal | Proceedings of the National Academy of Sciences of the United States of America | |
dash.depositing.author | Yuan, Junying::c7e832b918fc7c2356d6c49fe1a0b135::600 | |
dc.date.available | 2019-10-05T16:04:56Z | |
dash.workflow.comments | 1Science Serial ID 90170 | |
dc.identifier.doi | 10.1073/pnas.0802785105 | |
dash.source.volume | 105;18 | |
dash.source.page | 6584 | |