Featured Research

from universities, journals, and other organizations

Kinesin-5 structure opens cancer drug targets

Date:
April 8, 2014
Source:
University of California - Davis
Summary:
The structure of a key part of the machinery that allows cells to divide has been identified by researchers, opening new possibilities for throwing a wrench in the machine and blocking runaway cell division in cancer. "The structure of kinesin-5 is unexpected, and the implications are big -- it allows us to target it, for example in various forms of cancer," said the lead author.

The structure of a key part of the machinery that allows cells to divide has been identified by researchers at the University of California, Davis -- opening new possibilities for throwing a wrench in the machine and blocking runaway cell division in cancer.

"The structure of kinesin-5 is unexpected, and the implications are big -- it allows us to target it, for example in various forms of cancer," said Jawdat Al-Bassam, assistant professor of molecular and cellular biology at UC Davis, who led the project.

"This fills in a major missing piece, because for the first time we can understand how microtubule filaments can be linked together and slide past each other," he said.

The work will be published in the online journal eLife. When a cell divides into two new cells, a structure called the mitotic spindle forms. Microtubules of protein fan out from each end of the cell, capture chromosomes and draw them apart into what will become the two new cells. Precise coordination of this process is crucial for cells to divide properly, and for avoiding birth and developmental defects.

Cancer cells divide continuously, so this process repeats itself much more often in cancer cells than in normal cells.

The kinesins are a large family of motor proteins that move items around inside cells, said Jonathan Scholey, professor of molecular and cellular biology at UC Davis and an author on the paper. Generally, they have two motor units at one end that can "walk" along a microtubule, dragging cargo attached to the other end of the protein.

Originally identified as a protein essential for mitosis in fungi, kinesin-5 was first purified about 20 years ago by Scholey's lab who found that it is unusual because it has motor units at both ends, allowing it to link two microtubules and walk them past each other.

"It's now understood to be absolutely essential for mitosis in virtually all eukaryotic cells," Scholey said.

Using electron microscopy and X-ray crystallography, Al-Bassam, Scholey, Project Scientist Stanley Nithianantham and research specialist Jessica Scholey determined the atomic structure of the central rod of kinesin-5. They found that it is made up of four long helices of protein bundled together, two running in each direction.

"This is a much more intertwined structure than we thought it would be," Scholey said.

The structure also revealed "pockets" unique to kinesin-5 that could be exploited as targets for new anti-cancer drugs. Kinesin-5 has been identified as a target for drugs to treat cancers that involve uncontrolled cell division, such as colorectal cancer, Al-Bassam said. One such drug recently advanced as far as phase III clinical trials but ultimately was not approved for general use because of its effect on other motor proteins. Drugs that could target kinesin-5 more precisely by binding the newly identified pockets would be a big advance, he said.

The structure also explains how forces can be transmitted through the central rod between the end motor units, Al-Bassam said.

"Previously we had only a cartoon-level model of how this so-called 'sliding filament' mechanism works, but the new work takes it to the next level and opens up the possibility of learning how it really works at an atomic scale, which is exciting," Scholey said.


Story Source:

The above story is based on materials provided by University of California - Davis. Note: Materials may be edited for content and length.


Journal Reference:

  1. J. E. Scholey, S. Nithianantham, J. M. Scholey, J. Al-Bassam. Structural basis for the assembly of the mitotic motor Kinesin-5 into bipolar tetramers. eLife, 2014; 3 (0): e02217 DOI: 10.7554/elife.02217

Cite This Page:

University of California - Davis. "Kinesin-5 structure opens cancer drug targets." ScienceDaily. ScienceDaily, 8 April 2014. <www.sciencedaily.com/releases/2014/04/140408135034.htm>.
University of California - Davis. (2014, April 8). Kinesin-5 structure opens cancer drug targets. ScienceDaily. Retrieved August 21, 2014 from www.sciencedaily.com/releases/2014/04/140408135034.htm
University of California - Davis. "Kinesin-5 structure opens cancer drug targets." ScienceDaily. www.sciencedaily.com/releases/2014/04/140408135034.htm (accessed August 21, 2014).

Share This




More Health & Medicine News

Thursday, August 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Drug Used To Treat 'Ebola's Cousin' Shows Promise

Drug Used To Treat 'Ebola's Cousin' Shows Promise

Newsy (Aug. 21, 2014) An experimental drug used to treat Marburg virus in rhesus monkeys could give new insight into a similar treatment for Ebola. Video provided by Newsy
Powered by NewsLook.com
Cadavers, a Teen, and a Medical School Dream

Cadavers, a Teen, and a Medical School Dream

AP (Aug. 21, 2014) Contains graphic content. He's only 17. But Johntrell Bowles has wanted to be a doctor from a young age, despite the odds against him. He was recently the youngest participant in a cadaver program at the Indiana University NW medical school. (Aug. 21) Video provided by AP
Powered by NewsLook.com
American Ebola Patients Released: What Cured Them?

American Ebola Patients Released: What Cured Them?

Newsy (Aug. 21, 2014) It's unclear whether the American Ebola patients' recoveries can be attributed to an experimental drug or early detection and good medical care. Video provided by Newsy
Powered by NewsLook.com
Lost Brain Cells To Blame For Sleep Problems Among Seniors

Lost Brain Cells To Blame For Sleep Problems Among Seniors

Newsy (Aug. 21, 2014) According to a new study, elderly people might have trouble sleeping because of the loss of a certain group of neurons in the brain. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins