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Two proteins involved in the process that controls plant growth may help
explain why human cells reject chemotherapy drugs, according to an
international team of scientists, November 2005.

Researchers from Purdue University and Kyoto University in Japan have
shown for the first time that proteins similar to multi-drug resistant
proteins in humans move a plant growth hormone into cells, said Purdue plant
cell biologist Angus Murphy. Because plant proteins called P-glycoproteins
(PGPs) are closely related to human P-glycoproteins that impact chemotherapy
effectiveness, discovery of methods to control the plant protein's activity
may aid in development of therapies to reduce drug dosages administered to
cancer patients, Murphy said.

Murphy is corresponding author of the study published in the November issue
of Plant Cell. He also is corresponding author of a related article
published in October's Plant Journal.

"Results of this research will give us a better idea of the functioning of
the multi-drug resistance process in which human cancer cells reject
anticancer treatments," Murphy said.

Results of the two studies suggest a previously unknown relationship between
two protein families involved in this process, he said. Working together,
the proteins apparently move molecules of the plant growth hormone auxin
through cell walls. In humans, related proteins rid cells of toxins such as
cancer drugs.

"The findings of these two studies have important implications for
biomedicine because we now can identify the parts of these proteins that
determine whether cells take up or throw off different molecules, such as
cancer drugs," Murphy said.

In the Plant Journal study, Murphy and his collaborators at the University
of Zurich showed for first time that PGP1, a P-glycoprotein from the
commonly used experimental plant Arabidopsis, directly transports auxin out
of plant cells and also out of yeast and mammalian cells. In the Plant Cell
study, they found that other PGP proteins move auxin into cells.

"Auxin molecules essentially are pulled through the cell membrane by PGP
transport proteins," Murphy said. "It's an energetic process that happens
like pulling a rope through something sticky."

Both the multi-drug resistant PGPs in people and plants are part of a large
family of proteins, called ATP-binding cassette (ABC) proteins, that act as
delivery trucks to detoxify cells, send messages from cell to cell to
influence biochemical reactions, and to regulate those reactions. The ABC
proteins are so named because they must bind with ATP, the main cell energy
source, in order to fulfill their mission.

The best known member of another class of transport proteins, PIN1, also may
be a transporter, but appears to function primarily as an aide rather than
the delivery truck for auxin transport, Murphy said. This finding revealed
that PINs and PGPs may function together in long-distance auxin transport,
according to the Plant Journal article. Named for the pin-shaped appearance
of the mutant originally used to identify the gene that directs the
activities of PIN1, these proteins are members of the major protein family,
called facilators, that aid processes such as hormone transport.

Recent evidence suggests that teamwork between PGP and PIN proteins
determines the direction auxin moves and, therefore, how the plant develops,
Murphy said. In plants, shape, height and bending in response to light and
gravity are largely determined by the direction and amount of auxin moving
through their tissues.

Murphy and his collaborators on the Plant Journal study found that PGP1 and
PGP19 move the hormone out of cells.

In the November Plant Cell report, Murphy's research team reported that
another P-glycoprotein, PGP4, functions in the opposite direction, providing
the boost needed to import the hormone auxin into cells and to increase the
amount transported.

"With these two studies, we've shown for the first time that both the uptake
and release of molecules are mediated by interaction between the PGP
transporter proteins and PIN facilitator proteins," Murphy said.

Other researchers involved with the Plant Cell study were Joshua Blakeslee,
Wendy Peer, Boosaree Titapiwatanakun, Anindita Bandyopadhyay, Srinivas
Makam, Ok Ran Lee and Elizabeth Richards, all of the Purdue Department of
Botany and Plant Pathology; Kazuyoshi Teraska and Fumihiko Sato of the
Laboratory of Molecular & Cellular Biology of Totipotency, Kyoto University,
Japan; and Kazufumi Yazaki of the Laboratory of Plant Gene Expression, Kyoto
University. Teraska, Blakeslee and Titapiwatanakun each contributed equally
to the research project and as authors of the journal paper.

The U.S. National Science Foundation; the Ministry of Education, Culture,
Sports, Science and Technology of Japan; and the Uehara Foundation of
Kentucky provided support for this research.

On the Plant Journal paper, Markus Geisler of the Basel-Zurich Plant Science
Center, University of Zurich, and Blakeslee were co-lead authors and
contributed equally to the research; Murphy was corresponding author; and
Enrico Martinola, of the University of Zurich, was senior author. The U.S.
National Science Foundation and the Swiss National Science Foundation
provided funding for the study.

[news.uns.purdue.edu]

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