A BETTER picture of how cells divide and grow—the cell cycle—will
give us ways to control cancer and perhaps even replace missing limbs, says Marc
Kirschner, a cell biologist at Harvard University. Kirschner’s contribution to
this field is the paradoxical finding that cell creation depends crucially on
destruction.
In the early 1980s, protein destruction, or proteolysis, was thought of as
nothing more than a form of recycling. By dismantling the cell’s used or damaged
proteins, proteolysis ensured a continuous supply of building blocks for new
proteins. “This field was sort of sitting on the sidelines,” says Kirschner.
It turns out that proteins called cyclins build up gradually in the cell
until they reach a critical level, at which point they set off a series of
events leading to normal cell division—mitosis. Kirschner’s team found
that before the cell can finish mitosis it must chop up its cyclins.
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Most old proteins are recycled by enzyme-filled bags called lysosomes. But
cyclins are treated differently. First, tiny proteins called ubiquitins latch
onto the cyclins. Then a massive protein-eating machine called a proteasome
spots the ubiquitin flag and moves in for the kill.
One unanswered question is how cells know when to start destroying cyclins.
In the case of the cell cycle, a cluster of proteins called the
anaphase-promoting complex (APC) seems to be at the heart of the decision. The
APC’s job is to attach the ubiquitin tag to the cyclins.
A few months ago, Kirschner’s group found a short protein sequence common to
most known APC targets. He hopes this sequence will shed light on the regulation
of proteasome degradation. Already, Kirschner says, researchers have sent him
possible new regulatory functions for APC that they identified with his
sequence.
A better understanding of the signals in cell division could lead to ways of
correcting cell-cycle malfunctions such as cancer, Kirschner says. Doctors would
also like to be able to trick cells into dividing in response to artificial
signals. “I think we will figure out how to get cells to proliferate,” Kirschner
says. “That will lead to the ability to regenerate nerves, liver, heart muscle
and maybe limbs.” Salamanders can regenerate limbs, so we know it can be done.
“We’ve just got to figure out how to imitate that process,” he says.