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| Status |
Public on Apr 14, 2014 |
| Title |
A retinoblastoma allele that is mutated at its common E2F interaction site inhibits cell proliferation in gene targeted mice |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
The retinoblastoma protein (pRB) is best known for regulating cell proliferation through E2F transcription factors. In this report we investigate the properties of a targeted mutation that disrupts pRB interactions with the transactivation domain of E2Fs. Mice that carry this mutation endogenously (Rb1∆G) are defective in regulating E2F target genes. Surprisingly, cell cycle regulation in Rb1∆G/∆G MEFs strongly resembles that of wild type. In a serum deprivation induced cell cycle exit, Rb1∆G/∆G MEFs display a similar magnitude of E2F target gene derepression as Rb1-/-, even though Rb1∆G/∆G cells exit the cell cycle normally. Interestingly, cell cycle arrest in Rb1∆G/∆G MEFs is responsive to p16 expression, indicating that the ΔG-pRB protein can be activated in G1 to arrest proliferation through non-E2F mechanisms. Some Rb1∆G/∆G mice die neonatally with a muscle degeneration phenotype, while the others live a normal lifespan with no evidence of spontaneous tumor formation. Histological analysis reveals discrete examples of hyperplasia in the mammary epithelium, but most tissues appear normal while being accompanied by derepression of pRB regulated E2F targets. This suggests that non-E2F, pRB dependent pathways may have a more relevant role in proliferative control than previously identified.
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| Overall design |
Total RNA was extracted from littermate paired WT, ∆G and null MEFs induced to enter quiencense by Serum deprivation. Expresssion levels were analyzed by Affymetrix GeneChip Mouse Gene 1.0ST Array. Relative expression was determined by BRB-Array Tools software to generate RMA values.
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| Contributor(s) |
Thwaites MJ, Cantalupo P, Dick FA |
| Citation(s) |
24662053 |
| |
| Submission date |
Feb 12, 2014 |
| Last update date |
Mar 04, 2019 |
| Contact name |
Fred Dick |
| E-mail(s) |
fdick@uwo.ca
|
| Organization name |
Western University
|
| Street address |
Cancer Research Labs 790 Commissioners Road East
|
| City |
London |
| State/province |
ON |
| ZIP/Postal code |
N6A 4L6 |
| Country |
Canada |
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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 (9)
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| Relations |
| BioProject |
PRJNA238041 |
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