Adherent cells (left) or Rho-inhibited cells (bottom right) make cyclin D1 (red), but cells in suspension (top right) do not.

Assoian/Macmillan

Like romance, politics, and batting, cell division requires good timing. Now, a molecular switch that sets the pace for the early part of the cell cycle has been discovered. The switch is novel because it revs up one pathway, while blocking another that may accelerate the cell cycle.

A team led by Richard Assoian of the University of Pennsylvania (Philadelphia, PA) already knew that progression through the cell cycle depended on the protein cyclin D1. Induced during the middle of the G1 phase, cyclin D1 activates a cyclin-dependent kinase that advances the cell through the rest of that phase. Thus, cyclin D1 is vital to the timing of the cell cycle, says Assoian. “We view it as the event that sets the clock for the balance of the events that occur during G1 phase.” But how does the cell ensure that the cyclin D1 gene turns on at the right time? Assoian and colleagues determined that the master switch was a protein called Rho, which performs two functions. Rho is required for the activation of ERK MAP kinases, which are necessary for cyclin D1 expression in the middle of the G1 phase. The other function showed up when the authors inhibited Rho. Cyclin D1 turned on earlier in G1 phase, stimulated by an alternative pathway that Rho normally keeps silent. How Rho exerts control over the two pathways remains a mystery, Assoian says. He adds that the second pathway might allow the cell to shorten G1 phase and grow faster, although that possibility is unproven. “Rho might allow the cell to decide which pathway to turn on.” ▪

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