A new study published in the online open-access journal PLoS Biology explores a longstanding paradox in the regulation of a key tumor suppressor protein called p53. Min Hu, Yigong Shi, and their colleagues applied structural and mutational approaches to shed light on the regulation of a crucial regulatory pathway. Mutations that disable p53, which also plays a crucial role in regulating cell growth, are the most common mutations in many human cancers.
When cell damage occurs, p53 activates one of several stress-induced genes. In healthy cells, p53 levels are minimized by proteins that mark the protein for degradation such as MDM2. Intriguingly, by promoting the transcription of the MDM2 protein, p53 is responsible for its own regulation. Another protein that also plays a role in p53 regulation is an enzyme called HAUSP (herpesvirus-associated ubiquitin-specific protease) which can bind to p53, stabilize the protein, and promote cell death and cell growth arrest. But HAUSP can also stabilize MDM2. These seemingly contradictory actions led the researchers to wonder exactly what state p53 is left in once MDM2 and HAUSP have finished competing with one another.
Hu et al. show that both p53 and MDM2 bind to the same location on the HAUSP protein domain in a mutually exclusive manner. They also show that a conserved short amino acid signature appears to be responsible for this binding. Analysis of the molecular basis of their differential binding revealed that MDM2 binds HAUSP more frequently. And because MDM2 consistently formed stable complexes with HAUSP despite the presence of ten times more p53 peptides, it was clear that MDM2 binds to the HAUSP with a higher affinity. This suggests how HAUSP may regulate the critically important p53–MDM2 pathway.
Obstructing the ‘inner eye’
07.07.2017 | Friedrich-Schiller-Universität Jena
Drone vs. truck deliveries: Which create less carbon pollution?
31.05.2017 | University of Washington
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...
Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.
For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...
What is the mass of a proton? Scientists from Germany and Japan successfully did an important step towards the most exact knowledge of this fundamental constant. By means of precision measurements on a single proton, they could improve the precision by a factor of three and also correct the existing value.
To determine the mass of a single proton still more accurate – a group of physicists led by Klaus Blaum and Sven Sturm of the Max Planck Institute for Nuclear...
The research team of Prof. Dr. Oliver Einsle at the University of Freiburg's Institute of Biochemistry has long been exploring the functioning of nitrogenase....
A one trillion tonne iceberg - one of the biggest ever recorded -- has calved away from the Larsen C Ice Shelf in Antarctica, after a rift in the ice,...
21.07.2017 | Event News
19.07.2017 | Event News
12.07.2017 | Event News
24.07.2017 | Power and Electrical Engineering
24.07.2017 | Materials Sciences
24.07.2017 | Materials Sciences