Researchers headed by Joan Massagué at Memorial Sloan-Kettering Cancer Center (MSKCC) in New York and by María Macías at the Institute for Research in Biomedicine (IRB Barcelona) have identified a complex mechanism by which some proteins that are essential for life, called Smads, regulate the activity of genes associated with cancer.
The fruit of three years of intense work, the study reports on the life cycle of this protein, a process that ensures that the protein is destroyed when it has completed its function. These results have been published today in the top journal Genes & Development, which has devoted its cover to this research.
In the TGF-beta/Smad signal cascade, the hormones TGF-beta and BMP transmit information to the Smad protein in the cell nucleus in order for this molecule to stop cell division and to ensure that tissues grow in an orderly and coordinated manner. Although the TGF-beta/Smad signalling pathway has been known for over twenty years, until now it was unclear how Smads temporally controlled the activity of such important genes. “We had several pieces of the puzzle but we couldn’t put them together”, says Macías.
A number of earlier studies performed by Massagué’s lab had identified that Smads undergo phosphorylations –a kind of chemical change – in a region of the protein about which little is known. By means of biophysical and biochemical approaches, the researchers have discovered that these modifications occur in a coordinated fashion over time and are not random. “First, phosphorylations make some proteins bind to Smads in order to control the activity of target genes and later other phoshorylations cause protein bindings that lead to the destruction of Smad once this protein has completed its mission. This is the way cells prevent fatal errors”, explains Macías.
Having established the time sequence of these events, the scientists used cell and structural biology approaches –determination of the atom position in Smad proteins and other activating and destructor proteins bound to them– to confirm the results previously found. “We have been able to decipher the specificity of the binding between Smad and other proteins and to reveal the secret code that these proteins use to extract information”.
How do these proteins favour tumour cells? Massagué explains that “these signalling cascades are like the body’s pólice force. The tumour cells, in other words the delinquents, disturb these pathways and use them for their own means to grow and spread”. These pathways normally are involved in basic cell processes but when altered by mutations several diseases can appear such as cancer, congenital conditions, chronic inflammation and emphysema. These results could serve as the foundation on which to develop new clinical treatments against cancer and other diseases.
Genes & Development (2011). [doi: 10.1101/gad.2060811]
Nuria Noriega | EurekAlert!
Molecular Force Sensors
20.09.2017 | Max-Planck-Institut für Biochemie
Foster tadpoles trigger parental instinct in poison frogs
20.09.2017 | Veterinärmedizinische Universität Wien
Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...
Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!
When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...
For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.
Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...
MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems Holding GmbH about commercial use of a multi-well tissue plate for automated and reliable tissue engineering & drug testing.
MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems...
Pathogenic bacteria are becoming resistant to common antibiotics to an ever increasing degree. One of the most difficult germs is Pseudomonas aeruginosa, a...
19.09.2017 | Event News
12.09.2017 | Event News
06.09.2017 | Event News
20.09.2017 | Life Sciences
20.09.2017 | Power and Electrical Engineering
20.09.2017 | Physics and Astronomy