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Posted: Mar 06, 2013
New insight into double-protected dance of cell division
(Nanowerk News) Biochemists at the University of Massachusetts Amherst including assistant professor Peter Chien recently gained new insight into how protein synthesis and degradation help to regulate the delicate ballet of cell division. In particular, they reveal how two proteins shelter each other in “mutually assured cleanup” to insure that division goes smoothly and safely.
Cells must routinely dispose of leftover proteins with the aid of proteases that cut up and recycle used proteins. The problem for biochemists is that the same protein molecule can be toxic garbage at one time, but essential for function at another time such as during the cell cycle, that is, events that unfold to achieve replication of chromosomes and division of the cell.
To do this work, Amber Cantin in Chien’s lab, closely collaborated with Michael Laub and colleagues at MIT to look in a bacteria, Caulobacter, where they had previously figured out how cells distinguish waste proteins from useful molecules. They focused on a protein called CtrA that sits on DNA like a cap, controlling replication until conditions are right for division to occur.
Destruction of CtrA allows cells to start replicating their chromosome. Cantin used biochemical experiments with highly purified proteins to show that CtrA was only degraded when it was bound to DNA and that another protein, SciP, could help make CtrA bind better to DNA, making CtrA more resistant to proteolysis.
Surprisingly, this also made SciP less able to be destroyed as well, showing that both proteins prevent their own destruction by protecting each other. In addition, while both proteins were destroyed, they were recognized by completely different proteases. These advances, along with current findings, may offer medical researchers a clue for understanding diseases such as abnormal cell cycle progression in cancer.