Navigation Links
Kinesin-5 structure opens cancer drug targets
Date:4/8/2014

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 and is available at (elife website DOI)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.


'/>"/>

Contact: Andy Fell
ahfell@ucdavis.edu
530-752-4533
University of California - Davis
Source:Eurekalert

Related medicine news :

1. Males and females differ in specific brain structures
2. DNA-built nanostructures safely target, image cancer tumors
3. Brain structure shows who is most sensitive to pain
4. Bacterial Skin and Skin Structure Infections Market: SSSI Pipeline Review, H2 2013 at ReportsnReports.com
5. Polymer coatings based on molecular structures
6. NIH names leadership, research units for restructured HIV/AIDS
7. Heavy marijuana users have abnormal brain structure and poor memory
8. Skin And Skin Structure Infections (SSSI) Caused By Bacteria 2013
9. ZyDoc Links Philips SpeechExec Enterprise to MediSapien Structured Reporting and Analytics for Radiology at RSNA 2013
10. Middle East Critical Infrastructure Protection (CIP) Market (Technology, Solutions, Services) Worth $13.07 Billion by 2018 - New Report by MarketsandMarkets
11. Unique change in protein structure guides production of RNA from DNA
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/9/2016)... ... February 09, 2016 , ... Shark Finds and Kevin Harrington, and the Product Managers ... , GRIP-DRY is a newly patented product that has solved some of the basic problems ... and early morning dew or right after a rain shower, might understand the struggle of ...
(Date:2/8/2016)... ... February 08, 2016 , ... CURE Media Group , the nation’s ... Multiple Myeloma Heroes Awards event , which will annually honor individuals making heroic ... with MM. The MM Heroes Awards nomination process is officially open through ...
(Date:2/8/2016)... ... February 08, 2016 , ... Brenntag Specialties, Inc.(BSI) , ... Food & Beverage and Dietary Supplement market segments across the ... USA geographies east of the Rocky Mountains since 2012. Consistent performance in ...
(Date:2/8/2016)... ... 08, 2016 , ... Stephanie Hebert Insurance Agency, serving families ... new charity campaign. As part of their ongoing community involvement program, funds are ... that children deserve a voice, and in the spirit of neighbors helping neighbors ...
(Date:2/8/2016)... Angeles, CA (PRWEB) , ... February 08, 2016 , ... A man who has struggled ... of Freedom Laser Therapy , was determined to find solutions to his problems – ... of Inventors Digest is ready to introduce his breakthrough inventions to the world ...
Breaking Medicine News(10 mins):
(Date:2/8/2016)... , Feb. 8, 2016 CBG ... the PW Series Solvent Recycling Systems, specifically designed ... full integration with new and existing vapor degreasers, ... produces consistently-fresh solvent through continuous recycling and recovers ... --> --> Precision parts ...
(Date:2/8/2016)... 2016 --> ... "Ablation Technologies Market by Product (Radiofrequency, Ultrasound, Irreversible Electroporation, ... Surgery, Ophthalmology, Gynecology) - Global Forecasts to 2020", published ... the forecast period of 2015 to 2020. The market ... CAGR of 10.5% from 2015 to 2020. ...
(Date:2/8/2016)... EAST NORRITON, Pa. , Feb. 8, 2016 ... acquisition of November Research Group (NRG),s pharmacovigilance ... of pharmacovigilance system-related consulting services and an Oracle ... regulatory compliance services to Life Sciences companies. ... acquisition strengthens and expands HighPoint,s life sciences capabilities ...
Breaking Medicine Technology: