Plant's PICKLE gene may hold clue to cancer
WEST LAFAYETTE, Ind. Purdue University biochemist Joe Ogas set out to determine why pickle-shaped swellings developed on some laboratory plant roots. Instead, he stumbled upon a biochemical on/off switch that could help researchers better understand cancer and, at the same time, develop new oil crops.
"We were looking at genetically modified Arabidopsis plants, trying to understand root development," Ogas says. "What we found was something totally different that will help us understand how plant cells change identity. It will help explain how seeds throw a biochemical switch that turns them into seedlings."
Because the basic biochemistry behind cell development is similar in both plants and animals, Ogas' work attracted the attention of the National Institutes of Health (NIH). The NIH this spring awarded him a five-year, $1.1 million grant to pursue the biochemistry behind a single gene he discovered and named the "PICKLE gene" the gene that, when mutated, causes the root swellings. The results may help human health researchers understand and fight cancer, a disease in which cellular developmental controls go awry.
Ogas's work was published in a November 1999 article in the Proceedings of the National Academy of Sciences.
Based on his and other scientists' research, Ogas says plants depend on two biochemical switches as they change from seed to adult. He found that in germinating seeds with normal PICKLE genes, one switch turns on while the other turns off. The first switch turns on the development of characteristics for a mature plant, initiating root and shoot development. At the same time, the plant with the normal PICKLE gene produces a protein called chromatin remodeling factor, which flips the biochemical off-switch that stops the expression of embryo characteristics. The two switches operate independently.
In plants with an abnormal PICKLE gene, however, the plant can't make chromatin remodeling factor. Without that protein, it can't throw the off-switch to stop expression of embryo-like traits after seed germination. Because both biochemical switches are in the "on" position, the plants form roots, stems and leaves that act like a cross between embryo and adult. These plants produce storage proteins and oils just like seeds do, but store them in their roots. This creates the pickle-like root swellings that first caught Ogas's attention.
Now that the PICKLE gene has led Ogas to the switch, he's continuing to research the genetics behind it and to develop strategies that will allow researchers to turn it on and off. What he learns could help cancer researchers, he says, because research indicates that animals and humans also use the chromatin remodeling factor protein to turn certain genes on and off. Because cancerous cells have lost normal control of certain genetic on/off switches, the PICKLE gene could help us understand what's happening in human cancers, he says.
At the same time, Ogas is thinking about additional ways to make use of his discovery. For example, the ability to accumulate oil in plant roots someday may pay off for farmers.
"One of the next steps is finding out how to integrate the PICKLE characteristic into a crop," Ogas says. "Generally roots don't make oil. If you can use this gene to change that, to change the way a turnip, for example, thinks of itself, you might get roots that are productive in wonderfully new ways."
Ogas envisions a day when genetically modified turnips might produce more canola oil in an acre of roots than farmers can get out of seeds harvested from 10 acres of canola plants.
Source: Joe Ogas, 765-496-3969, email@example.com
Writer: Rebecca J. Goetz, 765-494-0461, firstname.lastname@example.org
Related Web sites:Proceedings of the National Academy of Sciences, Vol. 96, Issue 24
Joe Ogas*, Scott Kaufmann, Jim Henderson*, and Chris Somerville*, Department of Biochemistry, Purdue University, West Lafayette, IN 47907-1153; and Carnegie Institution of Washington, Department of Plant Biology, 260 Panama Street, Stanford, CA 94305)
The life cycle of angiosperms is punctuated by a dormant phase that separates embryonic and postembryonic development of the sporophyte. In the pickle (pkl) mutant of Arabidopsis, embryonic traits are expressed after germination. The penetrance of the pkl phenotype is strongly enhanced by inhibitors of gibberellin biosynthesis. Map-based cloning of the PKL locus revealed that it encodes a CHD3 protein. CHD3 proteins have been implicated as chromatin-remodeling factors involved in repression of transcription. PKL is necessary for repression of LEC1, a gene implicated as a critical activator of embryo development. We propose that PKL is a component of a gibberellin-modulated developmental switch that functions during germination to prevent reexpression of the embryonic developmental state.