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| Status |
Public on Feb 04, 2011 |
| Title |
C-JUN promotes BCR-ABL induced lymphoid leukemia by inhibiting methylation of the 5´ region of Cdk6 |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
The transcription factor c-JUN and its upstream kinase JNK1 have been implicated in BCR-ABL induced leukemogenesis. JNK1 has been shown to regulate BCL2 expression thereby altering leukemogenesis, but the impact of c-JUN remained unclear. In this study we show that JNK1 and c-JUN promote leukemogenesis via separate pathways, since lack of c-JUN impairs proliferation of p185BCR-ABL transformed cells without affecting viability. The decreased proliferation of c-JunD/D cells is associated with the loss of cyclin dependent kinase 6 (CDK6) expression. In c-JunD/D cells CDK6 expression becomes down-regulated upon BCR-ABL induced transformation which correlates with CpG island methylation within the 5´ region of Cdk6. We verified the impact of Cdk6 deficiency by using Cdk6-/- mice that developed BCR-ABL induced B-lymphoid leukemia with significantly increased latency and an attenuated disease phenotype. In addition we show that re-expression of CDK6 in BCR-ABL transformed c-JunD/D cells reconstitutes proliferation and tumor formation in Nu/Nu mice. In summary, our study reveals a novel function for the AP-1 transcription factor c-JUN in leukemogenesis by antagonizing promoter methylation. Moreover, we identify CDK6 as relevant and critical target of AP-1 regulated DNA methylation upon BCR-ABL induced transformation, thereby accelerating leukemogenesis.
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| Overall design |
Overall, 8 samples consisting of 4 wild type and 4 c-jun knock out samples were hybridized to MoGene-1_0-st-v1 microarrays.
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| Contributor(s) |
Sexl V, Kollmann K |
| Citation(s) |
21300982 |
| |
| Submission date |
Feb 02, 2011 |
| Last update date |
Sep 25, 2023 |
| Contact name |
Gerwin Heller |
| E-mail(s) |
[email protected]
|
| Organization name |
Medical University of Vienna
|
| Department |
Medicine I
|
| Street address |
Währinger Gürtel 18-20
|
| City |
Wien |
| ZIP/Postal code |
1090 |
| Country |
Austria |
| |
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| Platforms (1) |
| GPL6246 |
[MoGene-1_0-st] Affymetrix Mouse Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA137685 |
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