Navigation Links
UCLA researchers uncover new cell biological mechanism that regulates protein stability in cells
Date:12/23/2010

The cell signaling pathway known as Wnt, commonly activated in cancers, causes internal membranes within a healthy cell to imprison an enzyme that is vital in degrading proteins, preventing the enzyme from doing its job and affecting the stability of many proteins within the cell, researchers at UCLA's Jonsson Comprehensive Cancer Center have found.

The finding is important because sequestering the enzyme, Glycogen Synthase Kinase 3 (GSK3), results in the stabilization of proteins in the cell, at least one of which is known to be a key player in cancer, said Dr. Edward De Robertis, senior author of the study and a Jonsson Cancer Center scientist.

"Surprisingly, we found that the degradation of about 20 percent of proteins in the cell is triggered by the GSK3 enzyme," said De Robertis, who also is a Howard Hughes Medical Institute investigator. "That's a great many proteins and one of them, beta-Catenin, is known to cause cancer. We also know that Wnt signaling is activated in about 85 percent of colorectal cancers and other forms of cancer start with mutations that activate Wnt signaling. So, this finding could have ramifications for potential new treatments for cancer."

The study, a collaboration with cell biologist Dr. David D. Sabatini of New York University, appears in the Dec. 23, 2010 issue of the peer-reviewed journal Cell.

De Robertis said Wnt signaling requires inhibition of GSK3, but the enzyme sequestration mechanism was not known until now. The enzyme becomes imprisoned inside membrane-bounded organelles, known as multivesicular bodies, found within the cell cytoplasm.

"We knew these multivesicular bodies were involved in degradation of proteins, but that they had a role in how cells communicate with each other by switching on a signaling pathway was not known," De Robertis said. "This finding raises the possibility that other signaling pathways could operate through this sequestration mechanism."

When cells receive Wnt, it's a signal for cells to degrade their proteins more slowly, to keep them for a longer period of time because they're needed to regulate cell functions, such as proliferation. Wnt signaling, for example, is very high in all stem cells and rises during the regeneration of most tissues, De Robertis said.

"Perhaps one of the functions of Wnt is to stabilize certain cell functions and it may be that cancer needs higher protein stability than other cells, which is why increased Wnt signaling if found in so many cancers," De Robertis said. "These findings may give us new therapeutic targets for preventing sequestrations inside these membranes, which would decrease Wnt signaling."

De Robertis said this study also links two formerly unrelated areas of biology. The cell cytoplasm is filled with internal membranes that shuttle proteins to their final destinations. Cells in tissues communicate with their neighbors by receiving external signals called growth factors. The new work links the cell biology of membrane trafficking and the interpretation of the signals that control cell proliferation.

"Protein degradation is a very important part of the life of a cell. About 10 percent of the genes in the genome are dedicated to protein degradation," De Robertis said. "We now know that Wnt causes an enzyme that degrades proteins to be sequestered and because of that becomes a regulator of cellular protein stability."

De Robertis characterized this finding as "very unexpected."

"No one thought you could have cell signaling through sequestration of an enzyme inside a membrane organelle like these multivesicular bodies," he said. This is because the GSK3 enzyme is normally found everywhere in the cell, but becomes tightly bound to the internal side of membrane receptors when the Wnt signal is received.


'/>"/>

Contact: Kim Irwin
kirwin@mednet.ucla.edu
310-206-2805
University of California - Los Angeles
Source:Eurekalert  

Related medicine news :

1. Mount Sinai researchers make major breakthrough in melanoma research
2. Penn researchers identify potential target for breast cancer therapy
3. Researchers Turn White Fat to Energy-Burning Brown Fat in Mice
4. Finnish researchers find a compound that prevents the growth of prostate cancer cells
5. Ben-Gurion U. researchers: High resistance rates among acute otitis media pathogens in children
6. Breast inflammation is key to cancer growth, Kimmel Cancer Center researchers say
7. Researchers discover new signaling pathway linked to inflammatory disease
8. UCI researchers find novel memory-enhancing mechanism in brain
9. Researchers make critical leukemia stem cell discovery
10. U-M researchers discover way to block neurodegeneration in an adult form of Fragile X syndrome
11. Leibniz Prize 2011: 10 researchers awarded €2.5 million ($3.3 million) each
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
UCLA researchers uncover new cell biological mechanism that regulates protein stability in cells
(Date:6/27/2017)... ... June 27, 2017 , ... The Kelahan Agency, a ... to residents of southern New Hampshire, is teaming up with the New Horizons ... and homelessness in the region. , New Horizons for New Hampshire provides a ...
(Date:6/27/2017)... ... , ... Dr. Richard Amato, a respected periodontist in Monroe, CT, ... Implant Center of Connecticut. As part of the renovation, the cutting-edge practice added two ... to improve patient comfort while making it possible for Dr. Amato to provide even ...
(Date:6/27/2017)... ... 2017 , ... East Los Angeles dentist, Ramin Assili DDS , comments ... happens to a woman during pregnancy can have profound effects on a developing fetus, ... on a baby’s long-term health. This study, which was performed at the University of ...
(Date:6/26/2017)... California (PRWEB) , ... June 26, 2017 , ... ... of Male Fertility & Sexual Medicine Specialists, in collaboration with the Fertility Center ... for male fertility care: PESA (percutaneous epidydimal sperm aspiration) and TESA (percutaneous testicular ...
(Date:6/26/2017)... ... , ... LARKR™ , an innovative new smartphone app providing on-demand talk ... to join its online treatment platform. , Launching in just a few days, ... number of people in need nationwide, and to supplement their traditional practices. Joining this ...
Breaking Medicine News(10 mins):
(Date:6/20/2017)... Holdings, Inc. (NYSE: HRC), will host its fiscal third quarter ... 2017, beginning at 7:30 a.m. (CDT) / 8:30 a.m. (EDT). ... in the conference call, dial (877) 304-8969 (domestic) or (631) ... minutes prior to the start to allow time to connect. ... Webcast: A simultaneous webcast of the call will ...
(Date:6/16/2017)... 2017 Datascope Corp. is voluntarily performing a worldwide field correction ... electrical test failure code.     ... PART NUMBER ... 0998-UC-0446HXX; 0998-UC-0479HXX 0998-00-3013-XX;  ... This field correction also applies ...
(Date:6/14/2017)... 2017  ivWatch LLC, a medical device company focused ... therapy, is pleased to announce it was the Bronze ... Supplies and Equipment at the 2017 Medical Design Excellence ... industry. The award was presented by Medical Device and ... in New York during MD&M ...
Breaking Medicine Technology: