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| Status |
Public on Jun 01, 2016 |
| Title |
Prep1 and Meis1 competition for Pbx1 binding regulates protein stability and tumorigenesis [hP] |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Prep1 is a tumor-suppressor, whereas Meis1 is an oncogene. We show that to perform these activities in MEFs both proteins competitively hetero-dimerize with Pbx1. Meis1 alone transforms Prep1-deficient fibroblasts while Prep1 overexpression inhibits Meis1 tumorigenicity. Pbx1 can therefore alternatively act as oncogene or tumor-suppressor. Prep1 post-translationally controls the level of Meis1 decreasing its stability by sequestering Pbx1. The different levels of Meis1 and the presence of Prep1 are followed at the transcriptional level by the induction of specific transcriptional signatures. The decrease of Meis1 prevents Meis1 interaction with Ddx3x and Ddx5, which are essential for Meis1 tumorigenesis, and modifies the growth promoting DNA binding landscape of Meis1 to the growth controlling landscape of Prep1. Hence the key feature of Prep1 tumor inhibiting activity is the control of Meis1 stability.
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| Overall design |
Examination of Prep1 and Meis1 in two cell types
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| |
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| Contributor(s) |
Dardaei L, Blasi F |
| Citation(s) |
24578510 |
| |
| Submission date |
Jun 25, 2014 |
| Last update date |
May 15, 2019 |
| Contact name |
Francesco Blasi |
| E-mail(s) |
francesco.blasi@ifom.eu
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| Organization name |
IFOM
|
| Street address |
Via Adamello 16
|
| City |
Milan |
| ZIP/Postal code |
20139 |
| Country |
Italy |
| |
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| Platforms (1) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE82135 |
Prep1 and Meis1 competition for Pbx1 binding regulates protein stability and tumorigenesis |
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| Relations |
| BioProject |
PRJNA253530 |
| SRA |
SRP043551 |