Navigation Links
KEAP1 Keeps major cancer-promoting protein at bay
Date:10/9/2009

HOUSTON - A tumor-suppressing protein snatches up an important cancer-promoting enzyme and tags it with molecules that condemn it to destruction, a research team led by scientists at The University of Texas M. D. Anderson Cancer Center reports this week in the journal Molecular Cell.

"KEAP1 is a recently discovered tumor suppressor, but how it works has not been known. IKK is a known oncoprotein that promotes cancer in at least two different ways, but we did not know how it was regulated. We think we've answered both questions with this research," said senior author Mien-Chie Hung, Ph.D., chair and professor of M. D. Anderson's Department of Molecular and Cellular Oncology.

The researchers showed that KEAP1, short for the tongue-twisting Kelch-like ECH-associated protein 1, binds to IKK and attaches molecules known as ubiquitins to the oncoprotein, which targets it for dissolution by the cell's proteasome complex.

They also showed that underexpression of KEAP1 is associated with poor survival among breast cancer patients, and that it's mutated and inactivated in some breast, liver, lung and colon tumors.

"KEAP1 underexpression or inactivation is involved in multiple cancers, so we are working now to identify its activation mechanism, which could lead to development of new anti-cancer drugs," Hung said. He and his colleagues also want to know whether KEAP1 works on other known oncoproteins.

Blocking overexpression of IKK, short for IkB kinase , is crucial for at least two reasons. Hung and colleagues have shown that the protein inhibits at least two other important tumor suppressors. More importantly, IKK activates the NF?B (nuclear factor ?b) signaling pathway, which regulates expression of genes involved in the immune response, cellular proliferation, growth of new blood vessels, cell survival, tumor invasion, and the lethal spreading of cancer known as metastasis.

Hung and colleagues first demonstrated that the presence of KEAP1 inhibits the NF?B signaling pathway and then conducted a series of experiments to find out how that happens. They found that depletion of KEAP1 leads to the accumulation of IKK, and then discovered that the tumor suppressor binds to a specific site on IKK, capturing it to feed it to the proteasome.

Hung likens this snatching of IKK to plucking stuffed animals with a mechanical claw out of an arcade game, imagery that wound up on the cover of Molecular Cell.

KEAP1 is a ubiquitin ligase that attaches to the target protein and works in a complex with another protein, CUL3, that connects the ubiquitins to the bound protein.

The team analyzed both KEAP1 and CUL3 expression in the tumors of 119 breast cancer patients and correlated the findings to overall survival. They found that underexpression of KEAP1 alone was associated with poor survival. Patients with strong expression of both KEAP1 and CUL3 had an 80 percent survival rate at five years while those with little expression of either had a 43 percent 5-year survival rate.

Next, they sequenced KEAP1's genes in 26 cancer lines (18 breast, four liver, four lung) and in 119 primary tumors (17 breast, 78 liver, 13 lung, 11 colon) and found two functional genetic mutations that shut down the protein's ability regulate IKK. The mutations affected the portion of the protein that binds to IKK.


'/>"/>

Contact: Scott Merville
smerville@mdanderson.org
713-792-0661
University of Texas M. D. Anderson Cancer Center
Source:Eurekalert  

Related medicine news :

1. Exercise During Pregnancy Keeps Newborn Size Normal
2. Brain Training Keeps Older Drivers Safe Behind the Wheel
3. Peripheral Arterial Disease: Simple Quiz Keeps You Circulating
4. Good News for Elderly: Happiness Keeps Growing
5. Healthy Diet, Exercise Keeps Mind Sharp As You Age
6. Social Activity Keeps Elders Young, Agile
7. Stigma Keeps Teens From Depression Treatment
8. Drug Combo Keeps Kidney Artery-Vein Grafts Viable
9. Stress Keeps Americans Tossing and Turning
10. Diabetes Keeps Rising Among U.S. Adults
11. Simple Exercise Keeps Brain at Top of Its Game
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
KEAP1 Keeps major cancer-promoting protein at bay
(Date:3/24/2017)... , ... March 24, 2017 , ... ... of inspiring stories about real people of God in congregations across the United ... Miller, a Presbyterian minister ordained in 1964 who has served congregations in seven ...
(Date:3/23/2017)... Greensboro, NC & Seattle, WA (PRWEB) , ... March 23, 2017 ... ... international public health emergency and now estimates that there could be four million Zika-related ... fastest growing epidemics to date with numbers of US cases reported per year skyrocketing ...
(Date:3/23/2017)... Houston, Texas (PRWEB) , ... March 23, 2017 , ... ... their 3rd location in the greater Houston Area. The new location is located at ... St. Luke’s Hospital in Springwoods Village. This newest location will provide patients living in ...
(Date:3/23/2017)... ... March 23, 2017 , ... Texas Physical Therapy Specialists (TexPTS) ... Gruene Road in Building 2. The clinic is the group’s second in New Braunfels ... opening the company’s second New Braunfels location brings things full circle for the group, ...
(Date:3/23/2017)... ... 23, 2017 , ... The IoT (Internet of Things) is revolutionizing the way ... impact on businesses and individual consumers alike. Laboratories can maximize their profit margin ... anywhere from $4 trillion to $11 trillion dollars by the year 2025. McKinsey expects ...
Breaking Medicine News(10 mins):
(Date:3/24/2017)... , Mar. 24, 2017 Research and Markets ... Business Report" report to their offering. ... This report analyzes the worldwide markets for Dental Implants ... Canada , Japan , ... , and Rest of World. Annual estimates and ...
(Date:3/24/2017)... Mar. 24, 2017 Research and Markets has announced ... 2016" report to their offering. ... The IPF pipeline is very strong with a total of ... Co., Inc., Biogen and Sanofi are involved in the development of the ... one is in Phase III stage, 15 are in Phase II stage, ...
(Date:3/24/2017)... -- Research and Markets has announced the addition of ... report to their offering. ... The report provides separate comprehensive analytics for the US, Canada ... Asia-Pacific , Latin America , and ... 2015 through 2022. Also, a six-year historic analysis is provided for these ...
Breaking Medicine Technology: