Micro-management
The paper:
L. He et al., “A microRNA component of the p53 tumour suppressor network,” Nature, 447:1130–34, 2007. (Cited in 151 papers)
The finding:
Comparing wild-type mouse embryonic fibroblasts to cells lacking the cell cycle regulator p53, molecular biologist Gregory Hannon of Cold Spring Harbor Laboratory identified a family of microRNAs known as miR-34s whose transcription is directly regulated by p53. Overexpression of these microRNAs inhibited cell growth and caused cell cycle arrest, suggesting that the miR-34 family plays a critical role in the p53 tumor suppressor pathway.
The others:
In the summer of 2007, four other papers also independently confirmed that p53 controls miR-34 expression. Using different methodologies, these studies further highlighted miR-34’s effects on apoptosis and senescence, says Nikhil Chari, a molecular biologist at the MD Anderson Cancer Center in Houston, Texas. Hannon adds, “This raised a whole new class of...
The implication:
p53 “is regarded not only as a guardian of the genome but also a guardian against oncogenes,” says cancer biologist Heiko Hermeking of Ludwig-Maximilians-University of Munich, Germany. Identification of another mechanism by which p53 can downregulate target proteins provides a new set of possible targets for cancer therapies, Chari adds.
The next step:
Fewer than 10 of miR-34’s cellular targets have been validated. Chari suggests making knockout mouse models of miR-34 to discover the rest. “That will give you a better idea of what [miR-34] is doing,” he says.
| Increase in microRNA expression following DNA damage: | |
| miR-34a: 1180% | miR-34b: 2600% |
| miR-34c: 4570% | Average of 192 other miRNAs: 210% |
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