Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists Discover New Way Protein Degradation Is Regulated

29.04.2013
Proteins, unlike diamonds, aren’t forever. And when they wear out, they need to be degraded in the cell back into amino acids, where they will be recycled into new proteins.

Researchers at Rockefeller University and the Howard Hughes Medical Institute have identified a new way that the cell’s protein recycler, the proteasome, takes care of unwanted and potentially toxic proteins, a finding that has implications for treating muscle wasting, neurodegeneration and cancer.

The consensus among scientists has been that the proteasome is constantly active, chewing up proteins that have exceeded their shelf life. A mounting body of evidence now suggests that the proteasome is dynamically regulated, ramping up its activity when the cell is challenged with especially heavy protein turnover.

The researchers, postdoctoral associate Park F. Cho-Park and Hermann Steller, head of the Strang Laboratory of Apoptosis and Cancer Biology at Rockefeller, have shown that an enzyme called tankyrase regulates the proteasome’s activity. In addition, Cho-Park and Steller demonstrate that a small molecule called XAV939, originally identified by scientists at Novartis who developed it as therapeutic for colon cancer, inhibits tankyrase and blocks the proteasome’s activity. The research is reported in today’s issue of the journal Cell.

“Our findings have tremendous implications for the clinic since it gives a new meaning to an existing class of small-molecule compound,” says Steller, Strang Professor at Rockefeller and an investigator at HHMI. “In particular, our work suggests that tankyrase inhibitors may be clinically useful for treating multiple myeloma.”

Tankyrase was originally identified in the late 1990s by Rockefeller’s Titia de Lange and her colleagues in the Laboratory for Cell Biology and Genetics, who showed that it plays a role in elongating telomeres, structures that cap and protect the ends of chromosomes. In a series of experiments in fly and human cells, Cho-Park and Steller discovered that tankyrase uses a process called ADP-ribosylation to modify PI31, a key factor that regulates the activity and assembly of proteasome subunits into the active complex called 26S. By promoting the assembly of more 26S particles, cells under stress can boost their ability to break down and dispose of unwanted proteins.

The proteasome is currently a target for developing cancer therapeutics. The FDA has approved Velcade, a proteasome inhibitor, for the treatment of multiple myeloma and mantle cell lymphoma. However, patients on Velcade can experience peripheral neuropathy or become resistant to the drug.

Multiple myeloma cells need increased proteasome activity to survive. Preliminary data from Cho-Park and Steller show that XAV939 can block the growth of multiple myeloma cells by inhibiting the assembly of additional proteasomes without affecting the basal level of proteasomes in the cell. This selective targeting may mean fewer side effects for patients. “Drugs, such as XAV939, that inhibit the proteasome through other mechanisms than Velcade may have significant clinical value,” says Steller.

The findings by Cho-Park and Steller also link, for the first time, metabolism and regulation of the proteasome. Sometimes the proteasome digests too much protein, which can lead to loss of muscle, says Steller.

“This discovery reveals fundamental insights into protein degradation, a process important for normal cell biology, and a key factor in disorders such as muscle wasting and neurodegeneration,” said Stefan Maas of the National Institutes of Health’s National Institute of General Medical Sciences, which partly supported the study. “Intriguingly, the findings also enlighten ongoing research on cancer therapies, exemplifying the impact of basic research on drug development.”

Joseph Bonner | Newswise
Further information:
http://www.rockefeller.edu

More articles from Life Sciences:

nachricht Oestrogen regulates pathological changes of bones via bone lining cells
28.07.2017 | Veterinärmedizinische Universität Wien

nachricht Programming cells with computer-like logic
27.07.2017 | Wyss Institute for Biologically Inspired Engineering at Harvard

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Abrupt motion sharpens x-ray pulses

Spectrally narrow x-ray pulses may be “sharpened” by purely mechanical means. This sounds surprisingly, but a team of theoretical and experimental physicists developed and realized such a method. It is based on fast motions, precisely synchronized with the pulses, of a target interacting with the x-ray light. Thereby, photons are redistributed within the x-ray pulse to the desired spectral region.

A team of theoretical physicists from the MPI for Nuclear Physics (MPIK) in Heidelberg has developed a novel method to intensify the spectrally broad x-ray...

Im Focus: Physicists Design Ultrafocused Pulses

Physicists working with researcher Oriol Romero-Isart devised a new simple scheme to theoretically generate arbitrarily short and focused electromagnetic fields. This new tool could be used for precise sensing and in microscopy.

Microwaves, heat radiation, light and X-radiation are examples for electromagnetic waves. Many applications require to focus the electromagnetic fields to...

Im Focus: Carbon Nanotubes Turn Electrical Current into Light-emitting Quasi-particles

Strong light-matter coupling in these semiconducting tubes may hold the key to electrically pumped lasers

Light-matter quasi-particles can be generated electrically in semiconducting carbon nanotubes. Material scientists and physicists from Heidelberg University...

Im Focus: Flexible proximity sensor creates smart surfaces

Fraunhofer IPA has developed a proximity sensor made from silicone and carbon nanotubes (CNT) which detects objects and determines their position. The materials and printing process used mean that the sensor is extremely flexible, economical and can be used for large surfaces. Industry and research partners can use and further develop this innovation straight away.

At first glance, the proximity sensor appears to be nothing special: a thin, elastic layer of silicone onto which black square surfaces are printed, but these...

Im Focus: 3-D scanning with water

3-D shape acquisition using water displacement as the shape sensor for the reconstruction of complex objects

A global team of computer scientists and engineers have developed an innovative technique that more completely reconstructs challenging 3D objects. An ancient...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

Closing the Sustainability Circle: Protection of Food with Biobased Materials

21.07.2017 | Event News

»We are bringing Additive Manufacturing to SMEs«

19.07.2017 | Event News

 
Latest News

New 3-D imaging reveals how human cell nucleus organizes DNA and chromatin of its genome

28.07.2017 | Health and Medicine

Heavy metals in water meet their match

28.07.2017 | Power and Electrical Engineering

Oestrogen regulates pathological changes of bones via bone lining cells

28.07.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>