Featured Research

from universities, journals, and other organizations

Cancer Research: Biochemists Solve Structure Of TGF-beta And Its Receptor

Date:
February 27, 2008
Source:
University of Texas Health Science Center at San Antonio
Summary:
Researchers have determined the atomic-level structure of transforming growth factor-beta (TGF-beta), offering clues as to how it interlocks with cell receptors with which it has special affinity. This interaction plays an important role in normal cells but is especially important in cancer.

TGF-beta complex with its receptor subunits or interlocking 'puzzle pieces' (receptors labeled as TbRI and TbRII).
Credit: Image courtesy of University of Texas Health Science Center at San Antonio

Researchers from The University of Texas Health Science Center at San Antonio have determined the atomic-level structure of transforming growth factor-beta (TGF-β), offering clues as to how it interlocks with cell receptors with which it has special affinity. This interaction plays an important role in normal cells but is especially important in cancer.

Related Articles


TGF-β protein-receptor interaction promotes processes such as immune suppression, tissue remodeling and formation of blood vessels that lead to the growth and metastasis of cancer cells. The new finding, reported in the February issue of Molecular Cell, is being called a major milestone in the field and is expected to facilitate development of novel cancer therapies.

“TGF-β acts as a tumor suppressor in normal cells, but in cancer this growth-inhibiting capacity is selectively lost, and in turn TGF-β becomes a bad actor that induces many activities that lead to the growth and metastasis of cancer cells,” said corresponding author Andrew P. Hinck, Ph.D., professor in the Department of Biochemistry at the UT Health Science Center. “Understanding the detailed nature of the interactions between TGF-β and its receptors represents a critical new step forward, as this opens up the opportunity of finding new drugs that mimic the interactions between TGF-β and its receptors. These should block assembly of the TGF-β signaling complex and in turn eliminate TGF-β’s tumor-promoting activities.”

Although there are more than 40 other proteins like TGF-β in humans, none are able to bind the TGF-β receptors and hence none function in the same manner as TGF-β. “TGF-β is very selective in its interactions with its receptors, due to the fact that four receptor subunits bind in an interdependent manner, interacting not only with TGF-β but with one another as well. It is like a tight-fitting jigsaw puzzle that only goes together one way,” Dr. Hinck said.

“Although it was not previously appreciated by the broader scientific community, our results definitively demonstrate that TGF-β and the TGF-β receptors are very unique relative to related factors and their receptors,” he said. “In particular, other factors of this protein family bind their corresponding receptors independent of one another and without direct contact. This is fundamentally important since there are fewer constraints in terms of how the puzzle pieces fit together and, as such, these factors tend to ‘fit’ a much broader range of receptors compared to TGF-β.”

Cancer cells produce large amounts of TGF-β compared to normal cells. Many research groups are developing anti-TGF-β therapies to address disease situations in which the tumor-promoting activities are fueled by TGF-β over-expression, Dr. Hinck said. The current research may now allow these therapies to become much more targeted.

The finding drew the notice of a major voice in the TGF-β research field, Joan Massagué, Ph.D., of the Howard Hughes Medical Institute and Memorial Sloan-Kettering Cancer Center in New York. In a preview of the work published in the same issue of Molecular Cell, Dr. Massagué described how the “very private embrace” of TGF-β by its receptors creates an exquisite “selectivity mechanism that the work of Groppe et al (2008) so beautifully illustrates.”

Dr. Hinck joined the UT Health Science Center in 1997 and has studied TGF-β and its receptors since arriving in San Antonio. The work that culminated in the determination of the TGF-β receptor complex was carried out by Jay Groppe, Ph.D., a research assistant professor who previously carried out structural studies of other related molecules at the Salk Institute of Biomedical Sciences in La Jolla, Calif. “Jay’s efforts were critical to the successful completion of this project; a lot of the credit goes to him,” Dr. Hinck said.

The studies were carried out in the Department of Biochemistry at the UT Health Science Center and utilized the resources of the X-ray Crystallography Laboratory, which is directed by P. John Hart, Ph.D., and the Center for Surface Plasmon Resonance, which is directed by Eileen Lafer, Ph.D.


Story Source:

The above story is based on materials provided by University of Texas Health Science Center at San Antonio. Note: Materials may be edited for content and length.


Cite This Page:

University of Texas Health Science Center at San Antonio. "Cancer Research: Biochemists Solve Structure Of TGF-beta And Its Receptor." ScienceDaily. ScienceDaily, 27 February 2008. <www.sciencedaily.com/releases/2008/02/080223122241.htm>.
University of Texas Health Science Center at San Antonio. (2008, February 27). Cancer Research: Biochemists Solve Structure Of TGF-beta And Its Receptor. ScienceDaily. Retrieved December 18, 2014 from www.sciencedaily.com/releases/2008/02/080223122241.htm
University of Texas Health Science Center at San Antonio. "Cancer Research: Biochemists Solve Structure Of TGF-beta And Its Receptor." ScienceDaily. www.sciencedaily.com/releases/2008/02/080223122241.htm (accessed December 18, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Thursday, December 18, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Kids Die While Under Protective Services

Kids Die While Under Protective Services

AP (Dec. 18, 2014) — As part of a six-month investigation of child maltreatment deaths, the AP found that hundreds of deaths from horrific abuse and neglect could have been prevented. AP's Haven Daley reports. (Dec. 18) Video provided by AP
Powered by NewsLook.com
Dads-To-Be Also Experience Hormone Changes During Pregnancy

Dads-To-Be Also Experience Hormone Changes During Pregnancy

Newsy (Dec. 18, 2014) — A study from University of Michigan researchers found that expectant fathers see a decrease in testosterone as the baby's birth draws near. Video provided by Newsy
Powered by NewsLook.com
Prenatal Exposure To Pollution Might Increase Autism Risk

Prenatal Exposure To Pollution Might Increase Autism Risk

Newsy (Dec. 18, 2014) — Harvard researchers found children whose mothers were exposed to high pollution levels in the third trimester were twice as likely to develop autism. Video provided by Newsy
Powered by NewsLook.com
UN: Up to One Million Facing Hunger in Ebola-Hit Countries

UN: Up to One Million Facing Hunger in Ebola-Hit Countries

AFP (Dec. 17, 2014) — Border closures, quarantines and crop losses in West African nations battling the Ebola virus could lead to as many as one million people going hungry, UN food agencies said on Wednesday. Duration: 00:52 Video provided by AFP
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