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Duke Medical Team Identities Switch That Turns On And Off Cell Division
| Author: Tony Cappasso |
| Article Date: 3/25/2008 |
If there were a switch that a drug could turn off and so stop cell division, would that be a worthwhile target for drug development? Well, a team of Researchers from the Duke University Institute for Genome Sciences says they’ve discovered that switch. They publish their findings in the April issue of the journal Nature Biology.
The Duke team claims that their research shows that if the “divide” switch is on, cells will divide, even if they are damaged, giving some insight into why cancer cells continue to divide in the face of abnormality.
Cells pass a point in the run up to cell division, called the restriction point, the Duke team writes. Once the cell passes that point, it proceeds to divide and make a copy of itself, the authors say.
The switch is part of the Rb-E2F signaling pathway. Rb, or retinoblastoma, is a key tumor suppressor gene, and E2F is a transcription factor that governs the expression of all the genes important for cells to grow.
“The wiring diagram is fundamentally the same. It’s very likely that different organisms have evolved a very conserved design principle to regulate their growth,” said Guang Yao, Ph.D., lead study author and a postdoctoral fellow in Duke’s department of molecular genetics and microbiology.
The cellular pathway that includes the switch is found in all multi-cellular life, from plants to people. A cell decides to trigger the pathway when it receives an external chemical signal to grow.
During the project, the researchers discovered the switch has an unexpected property: it is bistable. Once turned on by an external signal, the switch can maintain its on state, even if the signal disappears.
This pathway, and this decision whether it is time to proliferate, is very tightly coupled to decisions of cell fate,” Nevins said. “There’s a decision as to whether the proliferation process is normal, and if the answer is not, then the result is that the cell dies. We don’t know critical dynamics of that process,” the researchers say.
The Duke team claims that their research shows that if the “divide” switch is on, cells will divide, even if they are damaged, giving some insight into why cancer cells continue to divide in the face of abnormality.
Cells pass a point in the run up to cell division, called the restriction point, the Duke team writes. Once the cell passes that point, it proceeds to divide and make a copy of itself, the authors say.
The switch is part of the Rb-E2F signaling pathway. Rb, or retinoblastoma, is a key tumor suppressor gene, and E2F is a transcription factor that governs the expression of all the genes important for cells to grow.
“The wiring diagram is fundamentally the same. It’s very likely that different organisms have evolved a very conserved design principle to regulate their growth,” said Guang Yao, Ph.D., lead study author and a postdoctoral fellow in Duke’s department of molecular genetics and microbiology.
The cellular pathway that includes the switch is found in all multi-cellular life, from plants to people. A cell decides to trigger the pathway when it receives an external chemical signal to grow.
During the project, the researchers discovered the switch has an unexpected property: it is bistable. Once turned on by an external signal, the switch can maintain its on state, even if the signal disappears.
This pathway, and this decision whether it is time to proliferate, is very tightly coupled to decisions of cell fate,” Nevins said. “There’s a decision as to whether the proliferation process is normal, and if the answer is not, then the result is that the cell dies. We don’t know critical dynamics of that process,” the researchers say.