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Investigating the Cell’s Garbage Disposal

Just as people clean up after dinner by running food scraps down the garbage disposal, cells get rid of proteins they no longer need by breaking them down with a special chemical pathway. Although a simple concept, a cell’s ability to clean house is very important, and it may hold the key to problems ranging from rotten tomatoes to cancer and Alzheimer’s disease.

Richard Vierstra, a University of Wisconsin-Madison researcher, has spent the last 20 years investigating this pathway, in which cells use the chemical ubiquitin to mark certain proteins for disposal–and he’s revealed some tantalizing secrets in the process.

“The ubiquitin pathway is instrumental for the development of humans and all plants and animals,” explains Vierstra, a professor of genetics in the College of Agricultural and Life Sciences. “Certain types of cancers result when the pathway fails, and when proteins accumulate and tangle neurons in the brain it causes Alzheimer’s disease. We’ve also found that ubiquitin plays a role in leaf death and fruit ripening.”

The ubiquitin pathway is so important that this year three scientists earned a Nobel Prize for their discovery that ubiquitin controls much of the process of protein degradation, Vierstra points out.

“We often use the phrase ‘birth, taxes and death’ to describe the human condition,” Vierstra observes, “but it seems that cells may live by the same creed. We already know that the birth and regulation–or taxation–of proteins are crucial life functions, and in the past few years we have begun to more fully understand protein death.”

The protein life cycle begins as cells monitor their environment for cues that tell them which proteins to build. Cells construct proteins to fight disease, transport nutrients and waste, and support organs, among other important jobs.

However, almost as fast as cells build proteins they must demolish them, using a chemical pathway–or what Vierstra calls a “molecular garbage disposal”–to chop up proteins that are no longer needed. When a cell gets a signal that a protein is not wanted it attaches a molecule called ubiquitin “like a Christmas tree ornament” to the protein to mark it for disposal.

After extraneous proteins are identified, structures called proteasomes pull flagged molecules inside and disassemble them into individual amino acids, which the cell can then use to build new proteins.

“At any given time, ten percent of the ten thousand or so proteins in a cell are being chopped up,” Vierstra explains. “A protein might function in a cell for only a matter of minutes before being marked with ubiquitin and degraded by proteasomes.”

Vierstra studies the ubiquitin pathway in a plant species called Arabidopsis, which comes from the same family as cabbage and radish. Researchers often use Arabidopsis because it grows quickly and is cheap to maintain, and also because previous work has decoded its entire genome, making gene identification easy. However, the ubiquitin pathway is so highly conserved across species that knowledge gained about plants can be applied to humans, Vierstra says.

In a recent experiment published in the Proceedings of the National Academy of Sciences, Vierstra showed a connection between the ubiquitin pathway and leaf death–called senescence–and fruit ripening. Plants cue these natural processes by producing the chemical ethylene–in fact, from ethylene comes the adage “one bad apple spoils the whole barrel,” because once one fruit starts producing ethylene and ripening it stimulates others nearby to make it as well.

The main trigger for ethylene response is a protein that cells constantly synthesize. However, in young plants the ubiquitin pathway degrades this protein so that no ethylene response occurs and the plant is able to grow. Eventually, ethylene blocks the breakdown and the key protein accumulates, triggering fruit to ripen and leaves to yellow and die.

Once Vierstra’s lab determines how the ethylene signal affects the ubiquitin pathway, they hope to learn how to control senescence and ripening to help farmers and grocery stores sell better quality fruits and vegetables. “We could block ripening during transportation from the field to the grocery store so that less fruit is wasted by becoming overripe,” Vierstra explains. “Some day, it could lead to the end of the rotten tomato!”