Unknown

Dataset Information

0

Activation of PI3K/Akt and MAPK pathways regulates Myc-mediated transcription by phosphorylating and promoting the degradation of Mad1.


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.

SUBMITTER: Zhu J 

PROVIDER: S-EPMC2373325 | biostudies-literature | 2008 May

REPOSITORIES: biostudies-literature

altmetric image

Publications

Activation of PI3K/Akt and MAPK pathways regulates Myc-mediated transcription by phosphorylating and promoting the degradation of Mad1.

Zhu Jidong J   Blenis John J   Yuan Junying J  

Proceedings of the National Academy of Sciences of the United States of America 20080501 18


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 su  ...[more]

Similar Datasets

| S-EPMC6138935 | biostudies-literature
| S-EPMC2783450 | biostudies-literature
| S-EPMC8167688 | biostudies-literature
| S-EPMC4807832 | biostudies-literature
| S-EPMC8939149 | biostudies-literature
| S-EPMC6888832 | biostudies-literature
| S-EPMC6725910 | biostudies-literature
| S-EPMC11542074 | biostudies-literature
| S-EPMC10539329 | biostudies-literature
| S-EPMC514509 | biostudies-literature