“We essentially found that cleanup in the cell is not supervised by one but by two proteins,” Groettrup says. “It is important because everything we know about this cleanup process assumes that only one enzyme initiates it. The second protein we discovered may either share some functions with the first one or do totally different things.”
The new study, to be published in the August 3 issue of the Journal of Biological Chemistry, was selected as a “Paper of the Week” by the journal’s editors, meaning that it belongs to the top one percent of papers reviewed in significance and overall importance.
Before being degraded, proteins are “tagged” with a small protein called ubiquitin. Three types of enzymes are involved in the tagging process. An enzyme called activating enzyme E1 first activates ubiquitin and binds to it. Then the ubiquitin is transferred to a second enzyme called ubiquitin-conjugating enzyme E2. And a third enzyme, called ubiquitin ligase E3 binds to both E2 and the protein to be degraded, so that E2 can transfer the ubiquitin to the protein. By binding to other ubiquitin-carrying E2 enzymes, E3 transfers many ubiquitins to the protein, signaling to the cell that the protein needs to be degraded.
Until now, only one type of E1 enzyme for ubiquitin has been known to exist in the human genome, while 34 E2 enzymes and 531 E3 enzymes have been discovered. Because of the large number of E2 or E3 enzymes that have been found, researchers are more likely to find another E2 or E3 enzyme than a new E1 enzyme, which explains why Goetrrup and his colleagues were very surprised to stumble upon one.
“You can picture E1 as the Federal Reserve Bank," Goettrup says. "Until now, scientists have shown that, in all the protein degradation processes that use ubiquitin, E1 is the master bank that distributes money (ubiquitin) to other banks (the E2 enzymes), which then give out credits to their clients (the E3 enzymes). What we found is another Federal Reserve Bank, bringing questions like: "What are the clients of this new master bank"' and 'Are there other master banks that we haven't found yet"' It makes us rethink protein degradation in completely new ways."
The scientists were searching for an enzyme similar to E1 that activates a protein that looks like ubiquitin called FAT10. Surprisingly, the enzyme they found could not activate FAT10 but instead activated ubiquitin itself. The researchers then tested whether this enzyme, which they called UBE1L2, also helped degrade proteins by working with E2 and E3 enzymes. They confirmed that this was indeed the case.
Groettrup and his team also tested whether UBE1L2 was – like the original E1 – expressed in all organs and tissues. They measured the expression levels of UBE1L2 in mice and found that the protein was expressed about five times more in the testis than other organs.
“Again, this was totally unexpected,” Goettrup says. “Unlike the first E1, UBE1L2 might have a specialized role in tissues and in particular in the testis. Going back to the previous analogy of the Federal Reserve Bank, this result shows that UBE1L2’s ‘main client banks’ may be in the testis and that UBE1L2 controls many of the protein degradation processes in that organ.”
Goettrup and colleagues are now planning to investigate which E2 and E3 enzymes work with UBE1L2 and determine whether they also work with the original E1. The scientists also would like to investigate a potential role for UBE1L2 in male fertility and determine why the enzyme is more highly expressed in testes than in ovaries.
ARTICLE: “UBE1L2, a novel E1 enzyme, specific for Ubiquitin,” by Christiane Pelzer, Ingrid Kassner, Konstantin Matentzoglu, Rajesh K. Singh, Hans-Peter Wollscheid, Martin Scheffner, Gunter Schmidtke, and Marcus Groettrup
MEDIA CONTACT: Marcus Groettrup, University of Constance, Konstanz, Germany; tel. +49 7531 88 2130; e-mail: firstname.lastname@example.org
The American Society for Biochemistry and Molecular Biology is a nonprofit scientific and educational organization with over 11,900 members in the United States and internationally. Most members teach and conduct research at colleges and universities. Others conduct research in various government laboratories, nonprofit research institutions and industry. The Society’s student members attend undergraduate or graduate institutions.
Founded in 1906, the Society is based in Bethesda, Maryland, on the campus of the Federation of American Societies for Experimental Biology. The Society's purpose is to advance the science of biochemistry and molecular biology through publication of the Journal of Biological Chemistry, the Journal of Lipid Research, and Molecular and Cellular Proteomics, organization of scientific meetings, advocacy for funding of basic research and education, support of science education at all levels, and promoting the diversity of individuals entering the scientific work force.
Pat Pages | EurekAlert!
Exploring how herpes simplex virus changes when passed between family members
23.10.2017 | Penn State
Key discoveries offer significant hope of reversing antibiotic resistance
23.10.2017 | University of Bristol
University of Maryland researchers contribute to historic detection of gravitational waves and light created by event
On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...
Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.
Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....
Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).
When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...
Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.
How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...
Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.
It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...
23.10.2017 | Event News
17.10.2017 | Event News
10.10.2017 | Event News
23.10.2017 | Press release
23.10.2017 | Physics and Astronomy
23.10.2017 | Earth Sciences