Featured Research

from universities, journals, and other organizations

Assembly of a protein degradation machine could lead to treatments in cancer, neurological diseases

Date:
May 6, 2013
Source:
Kansas State University
Summary:
Scientists have discovered new details about an assembly intricate process in cells and the proteins named chaperones that controls it. Their finding may advance treatments for cancer and neurological diseases.

A computer model of the regulatory particle and core particle docking process that is controlled by chaperones.
Credit: Image courtesy of Kansas State University

Kansas State University scientists helped discover new details about an intricate process in cells. Their finding may advance treatments for cancer and neurological diseases.

Related Articles


Kansas State University researchers Jeroen Roelofs, assistant professor, and Chingakham Ranjit Singh, research assistant professor -- both in the Division of Biology -- led part of the study. Both also are research affiliates with the university's Johnson Cancer Research Center. They worked with colleagues at Harvard Medical School, the University of California-San Francisco and the University of Kansas. The scientific journal Nature recently published the team's observations, titled "Reconfiguration of the proteasome during chaperone-mediated assembly."

The research focused on proteasomes, protein complexes inside the cells of humans and other organisms that help keep the cells healthy.

"The proteasome is a large, molecular machine in the cell that degrades other proteins," Roelofs said. "It's important for protein quality control as well as for the cell's ability quickly remove specific proteins, thereby ensuring the cell's health and proper function."

The goal was to better understand how the various particles inside proteasomes work together to make the proteasomes function -- think the gears and components needed, and in what order, to build a working machine. Scientists believe that disruption of two key particles -- and consequently a proteasome's ability to work correctly -- has implications for cancers as well as various neurological degenerative diseases, such as Parkinson's and Huntington's diseases.

The Nature study built on research that Roelofs made as a postdoctoral research fellow at Harvard Medical School in 2009. He found that proteins called chaperones play a key role in the assembly process of two particles that when connected, gives proteasomes the ability to scrub unwanted proteins from cells. Chaperones act as a foreman for the two particles.

One of the findings in the new study is that in addition to acting as a molecular foreman for the two particles, chaperones also control when those two particles come together. Similarly, the scientists found more about the two particles.

The core particle has seven pockets while the regulatory particle has six tails that tuck into those pockets. When docked together, they turn on the proteasome's functionality.

"In the assembly process there is only one tail that actually determines how the core particle and regulatory particle bind together," Roelofs said. "That's surprising because there are six tails, but only one is needed to give specificity, and the docking into the pocket is controlled by the chaperone."

Roelofs believes that the findings may reveal new targets for anticancer drugs, as a chaperone in the human genes is involved in liver cancer. The proteasome inhibitor Bortezomib is used in the treatment of current cancers. Additionally, the information may advance cancer and neurological research by giving scientists new pathways to study and manipulate.

"This is pretty basic research," Roelofs said. "Understanding the basic mechanics can often lead to new pathways for improvement, which is essential when it comes to human health."

Scientists made the findings through a combination of techniques, including Cryo-electron microscopy, X-ray crystallography, yeast genetics, biochemical reconstitution assays and proteasome activity measurements. These techniques helped researchers observe the submicroscopic tails and complex tail-to-pocket binding process, as well as study the role of the chaperones in the core and regulatory particle process.

The study was largely funded by the Centers of Biomedical Research Excellence Protein Structure and Function, or COBRE-psf, support center at the University of Kansas -- a multidisciplinary, biomedical research program funded by the National Institute of Health; the Johnson Cancer Research Center at Kansas State University; and the Kansas IDeA Network of Biomedical Research Excellence, or K-INBRE.


Story Source:

The above story is based on materials provided by Kansas State University. Note: Materials may be edited for content and length.


Journal Reference:

  1. Soyeon Park, Xueming Li, Ho Min Kim, Chingakham Ranjit Singh, Geng Tian, Martin A. Hoyt, Scott Lovell, Kevin P. Battaile, Michal Zolkiewski, Philip Coffino, Jeroen Roelofs, Yifan Cheng, Daniel Finley. Reconfiguration of the proteasome during chaperone-mediated assembly. Nature, 2013; DOI: 10.1038/nature12123

Cite This Page:

Kansas State University. "Assembly of a protein degradation machine could lead to treatments in cancer, neurological diseases." ScienceDaily. ScienceDaily, 6 May 2013. <www.sciencedaily.com/releases/2013/05/130506094922.htm>.
Kansas State University. (2013, May 6). Assembly of a protein degradation machine could lead to treatments in cancer, neurological diseases. ScienceDaily. Retrieved November 27, 2014 from www.sciencedaily.com/releases/2013/05/130506094922.htm
Kansas State University. "Assembly of a protein degradation machine could lead to treatments in cancer, neurological diseases." ScienceDaily. www.sciencedaily.com/releases/2013/05/130506094922.htm (accessed November 27, 2014).

Share This


More From ScienceDaily



More Plants & Animals News

Thursday, November 27, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Classic Hollywood Memorabilia Goes Under the Hammer

Classic Hollywood Memorabilia Goes Under the Hammer

Reuters - Entertainment Video Online (Nov. 26, 2014) The iconic piano from "Casablanca" and the Cowardly Lion suit from "The Wizard of Oz" fetch millions at auction. Sara Hemrajani reports. Video provided by Reuters
Powered by NewsLook.com
Pet Dogs to Be Used in Anti-Ageing Trial

Pet Dogs to Be Used in Anti-Ageing Trial

Reuters - Innovations Video Online (Nov. 26, 2014) Researchers in the United States are preparing to discover whether a drug commonly used in human organ transplants can extend the lifespan and health quality of pet dogs. Video provided by Reuters
Powered by NewsLook.com
From Popcorn To Vending Snacks: FDA Ups Calorie Count Rules

From Popcorn To Vending Snacks: FDA Ups Calorie Count Rules

Newsy (Nov. 25, 2014) The US FDA is announcing new calorie rules on Tuesday that will require everywhere from theaters to vending machines to include calorie counts. Video provided by Newsy
Powered by NewsLook.com
Feast Your Eyes: Lamb Chop Sent Into Space from UK

Feast Your Eyes: Lamb Chop Sent Into Space from UK

Reuters - Light News Video Online (Nov. 25, 2014) Take a stab at this -- stunt video shows a lamb chop's journey from an east London restaurant over 30 kilometers into space. Rough Cut (no reporter narration). Video provided by Reuters
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:

Strange & Offbeat Stories


Plants & Animals

Earth & Climate

Fossils & Ruins

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