Featured Research

from universities, journals, and other organizations

Discovery of relationship between proteins may impact development of cancer therapies

Date:
April 24, 2011
Source:
University of Iowa Health Care
Summary:
By identifying a surprising association of two intracellular proteins, researchers have laid the groundwork for the development of new therapies to treat B cell lymphomas and autoimmune disease.

By identifying a surprising association of two intracellular proteins, University of Iowa researchers have laid the groundwork for the development of new therapies to treat B cell lymphomas and autoimmune disease.

The researchers studied mouse B cells expressing the viral protein Latent Membrane Protein 1 (LMP1), which has been implicated in several types of cancer because of its role in the proliferation and survival of Epstein-Barr virus infected B cells. They discovered that LMP1 needs the cellular protein Tumor Necrosis Factor Receptor-Associated Factor 6 (TRAF6) to promote its B cell activation signaling pathways.

The study, published recently in the Journal of Biological Chemistry, also shows that LMP1 and CD40 -- a normal activating receptor of B cells -- both use TRAF6 as a key signaling protein, but in different ways. LMP1 mimics CD40 in delivering activation signals to B cells, but LMP1's signals are amplified and sustained, resulting in B cell hyper-activation.

B cells are a type of white blood cell. They normally mature into plasma cells that produce proteins called antibodies necessary to fight off infections. But in the process of modifying antibody genes, mistakes can cause mutations. With an accumulation of such mutations, B cells can become cancerous, which is why B cell malignancies are relatively common.

"We found that TRAF6 is essential for LMP1 functions, and that it interacts with LMP1 in a way that is distinct from the way in which TRAF6 interacts with CD40," said lead author Kelly Arcipowski, a Ph.D. candidate in the UI Molecular and Cellular Biology Interdisciplinary Graduate Program. "Thus, it might be possible to target LMP1 signaling without disrupting normal immune function. This information is valuable to the development of new therapies to target LMP1-mediated pathogenesis, including B cell lymphomas and autoimmune disease."

B-cell lymphomas include Hodgkin's lymphomas and most non-Hodgkin's lymphomas. Examples of autoimmune diseases in which LMP1 is implicated are rheumatoid arthritis and systemic lupus erythematosus (SLE).

LMP1 is produced by a normally latent gene that is expressed when Epstein-Barr virus, a herpes virus that infects greater than 90 percent of humans, becomes reactivated from its inactive state. This can occur in flares of autoimmune disease, and in people who are immune-deficient. Epstein-Barr virus can thus become activated in cases of late-stage AIDS or organ and bone marrow transplant recipients who are immunosuppressed to prevent rejection of the transplant.

While LMP1 contributes to the formation of a tumor, it isn't an ideal target for therapeutics. LMP1 is a protein that is being constantly internalized from the cell surface, prompting researchers to instead target the signaling pathway.

"(Researchers) first thought you would be targeting the normal protein (CD40), too," said senior study author Gail Bishop, Ph.D., professor of microbiology at the UI Carver College of Medicine and director of the Immunology Interdisciplinary Graduate Program. "What our lab has discovered over the years is that LMP1 produces CD40-like effects using the same proteins in different ways, and therefore that opens a window to targeting just LMP1."

Arcipowski currently is researching how TRAF6 is activating the LMP1 signaling pathway.

"If you figured out exactly which part of TRAF6 was binding to LMP1, you could target that specific interaction while leaving TRAF6's association with CD40 intact," Arcipowski said.

The research team included Bishop and her lab members Arcipowski, Laura Stunz (Microbiology), John Graham (Immunology), Zachary Kraus (Immunology) and Tony Vanden Bush (Microbiology).

The study was funded by a National Institutes of Health grant and by the American Heart Association.


Story Source:

The above story is based on materials provided by University of Iowa Health Care. Note: Materials may be edited for content and length.


Journal Reference:

  1. K. M. Arcipowski, L. L. Stunz, J. P. Graham, Z. J. Kraus, T. J. V. Bush, G. A. Bishop. Molecular Mechanisms of TNFR-associated Factor 6 (TRAF6) Utilization by the Oncogenic Viral Mimic of CD40, Latent Membrane Protein 1 (LMP1). Journal of Biological Chemistry, 2011; 286 (12): 9948 DOI: 10.1074/jbc.M110.185983

Cite This Page:

University of Iowa Health Care. "Discovery of relationship between proteins may impact development of cancer therapies." ScienceDaily. ScienceDaily, 24 April 2011. <www.sciencedaily.com/releases/2011/04/110419101245.htm>.
University of Iowa Health Care. (2011, April 24). Discovery of relationship between proteins may impact development of cancer therapies. ScienceDaily. Retrieved October 22, 2014 from www.sciencedaily.com/releases/2011/04/110419101245.htm
University of Iowa Health Care. "Discovery of relationship between proteins may impact development of cancer therapies." ScienceDaily. www.sciencedaily.com/releases/2011/04/110419101245.htm (accessed October 22, 2014).

Share This



More Health & Medicine News

Wednesday, October 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

CDC Revamps Ebola Guidelines After Criticism

CDC Revamps Ebola Guidelines After Criticism

Newsy (Oct. 21, 2014) The Centers for Disease Control and Prevention have issued new protocols for healthcare workers interacting with Ebola patients. Video provided by Newsy
Powered by NewsLook.com
WHO: Ebola Vaccine Trials to Start a in January

WHO: Ebola Vaccine Trials to Start a in January

AP (Oct. 21, 2014) Tens of thousands of doses of experimental Ebola vaccines could be available for "real-world" testing in West Africa as soon as January as long as they are deemed safe in soon to start trials, the World Health Organization said Tuesday. (Oct. 21) Video provided by AP
Powered by NewsLook.com
First-Of-Its-Kind Treatment Gives Man Ability To Walk Again

First-Of-Its-Kind Treatment Gives Man Ability To Walk Again

Newsy (Oct. 21, 2014) A medical team has for the first time given a man the ability to walk again after transplanting cells from his brain onto his severed spinal cord. Video provided by Newsy
Powered by NewsLook.com
CDC Issues New Ebola Guidelines for Health Workers

CDC Issues New Ebola Guidelines for Health Workers

Reuters - US Online Video (Oct. 21, 2014) The U.S. Centers for Disease Control and Prevention has set up new guidelines for health workers taking care of patients infected with Ebola. Linda So reports. 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


Health & Medicine

Mind & Brain

Living & Well

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