Corpus Curare Spiritumque
Over the past ten years, several pieces of the puzzle that immunity signal controls have been met. Now, in an international group of cells indicates a paradigm shift in the regulation of the immune response. Their results show that interaction with a linear ubiquitin chain is crucial for the nuclear factor kappa B activation. Your knowledge can also contribute to the structure-based drug development in the absence of NF-κB path of diseases such as cancer, inflammation and immune weakness.
The position of first line of defense against bacteria and viruses, the innate immune system, where cells macrophages, and foreign body reaction of alarm, often accompanied by inflammation. Accordingly, the molecular signals in the blood, such as receptors of the tumor factor (TNF) or interleukin-1, and the reaction of the immune system. But what happens if the molecular signals are anchored to the cell receptors that are specialized in the immune response? What is the basis of signaling by cell receptors within the cell membrane?
Over the past ten years, the overall picture of this puzzle has been gradually rebuilding to show that changes in cell proteins – including the addition of phosphate groups (phosphorylation), or the combination of small changes ubiquitin (Ubiquitinierung) – play a central role in controlling the immune system.
Scientists at the Goethe University in Frankfurt under the direction of Professor Ivan DIKIC have international cooperation to investigate the role of the ubiquitin modification of these methods. The international team consists of the laboratories of the Soichi WAKATSUKI (Photon Factory, Tsukuba, Japan), Fumiyo Ikeda (Medili, Split, Croatia), Felix Randow (LMB, Cambridge, UK) and David Komanda (LMB, Cambridge, UK ). They studied as a transcription factor known as nuclear factor kappa B (NF-κB) is coordinating the expression of genes, cells of the immune response. NF-κB by an enzyme (IkappaB kinase, IKK), a regulatory subunit, which recalls the enigmatic captain, Jules Verne science-fiction novels: Nemo.
The question to answer, as NEMO does not activate NF-κB? This is the work of biochemists in Frankfurt was up a sub-domain of NEMO, has requested that the city selectively binds to a certain type of ubiquitin. This protein is ubiquitous in the cell, and has several functions, the molecular diversity of the signal. It may as molecule (monoubiquitin) or as strings (polyubiquitin).
In the journal “Cell”, Ivan DIKIC and his colleagues report that NEMO binds to specific chains of ubiquitin-linear and it is an essential step for the activation of NF-κB. It was a great surprise for the team because he thought before other types of ubiquitin signals were essential for NEMO-dependent NF-κB activation. “This leads to a paradigm shift,” says Ivan DIKIC, “this means that the current knowledge on the activation of NF-κB and the role of the ubiquitin-linear chains must be updated.
In collaboration with the group Soichi Wakatsuki, NEMO, the structure could be resolved. The work shows that the urban binds to a linear chain of ubiquitin locking and principle. “This new knowledge not only explain the details of the nuclear ubiquitin chain selectivity, but also useful in the development of targeted therapies for the promotion of the track NF-κB,” said Soichi WAKATSUKI. Strengthening the Enabling towards NF-κB is known that in the development of several diseases such as cancer and inflammation.
The discovery also direct medical relevance. “We are pleased that this basic scientific discovery may explain the harmful effects of NEMO mutations in patients with chromosome X-ectodermal dysplasia and a weak immune system,” says Ivan DIKIC. Ectodermal dysplasia is an inherited disorder, children from 1 to 5 in 10,000 newborns. It allows the very thin skin and glands perspiratory of operating problems. In some cases it is associated with immunodeficiency. The molecular defect is a mutation of the NEMO gene, which blocks the activation of NF-κB path in the epidermal and immune cells.
Over the past ten years, several pieces of the puzzle that immunity signal controls have been met. Now, in an international group of cells indicates a paradigm shift in the regulation of the immune response. Their results show that interaction with a linear ubiquitin chain is crucial for the nuclear factor kappa B activation. Your knowledge can also contribute to the structure-based drug development in the absence of NF-κB path of diseases such as cancer, inflammation and immune weakness.
The position of first line of defense against bacteria and viruses, the innate immune system, where cells macrophages, and foreign body reaction of alarm, often accompanied by inflammation. Accordingly, the molecular signals in the blood, such as receptors of the tumor factor (TNF) or interleukin-1, and the reaction of the immune system. But what happens if the molecular signals are anchored to the cell receptors that are specialized in the immune response? What is the basis of signaling by cell receptors within the cell membrane?
Over the past ten years, the overall picture of this puzzle has been gradually rebuilding to show that changes in cell proteins – including the addition of phosphate groups (phosphorylation), or the combination of small changes ubiquitin (Ubiquitinierung) – play a central role in controlling the immune system.
Scientists at the Goethe University in Frankfurt under the direction of Professor Ivan DIKIC have international cooperation to investigate the role of the ubiquitin modification of these methods. The international team consists of the laboratories of the Soichi WAKATSUKI (Photon Factory, Tsukuba, Japan), Fumiyo Ikeda (Medili, Split, Croatia), Felix Randow (LMB, Cambridge, UK) and David Komanda (LMB, Cambridge, UK ). They studied as a transcription factor known as nuclear factor kappa B (NF-κB) is coordinating the expression of genes, cells of the immune response. NF-κB by an enzyme (IkappaB kinase, IKK), a regulatory subunit, which recalls the enigmatic captain, Jules Verne science-fiction novels: Nemo.
The question to answer, as NEMO does not activate NF-κB? This is the work of biochemists in Frankfurt was up a sub-domain of NEMO, has requested that the city selectively binds to a certain type of ubiquitin. This protein is ubiquitous in the cell, and has several functions, the molecular diversity of the signal. It may as molecule (monoubiquitin) or as strings (polyubiquitin).
In the journal “Cell”, Ivan DIKIC and his colleagues report that NEMO binds to specific chains of ubiquitin-linear and it is an essential step for the activation of NF-κB. It was a great surprise for the team because he thought before other types of ubiquitin signals were essential for NEMO-dependent NF-κB activation. “This leads to a paradigm shift,” says Ivan DIKIC, “this means that the current knowledge on the activation of NF-κB and the role of the ubiquitin-linear chains must be updated.
In collaboration with the group Soichi Wakatsuki, NEMO, the structure could be resolved. The work shows that the urban binds to a linear chain of ubiquitin locking and principle. “This new knowledge not only explain the details of the nuclear ubiquitin chain selectivity, but also useful in the development of targeted therapies for the promotion of the track NF-κB,” said Soichi WAKATSUKI. Strengthening the Enabling towards NF-κB is known that in the development of several diseases such as cancer and inflammation.
The discovery also direct medical relevance. “We are pleased that this basic scientific discovery may explain the harmful effects of NEMO mutations in patients with chromosome X-ectodermal dysplasia and a weak immune system,” says Ivan DIKIC. Ectodermal dysplasia is an inherited disorder, children from 1 to 5 in 10,000 newborns. It allows the very thin skin and glands perspiratory of operating problems. In some cases it is associated with immunodeficiency. The molecular defect is a mutation of the NEMO gene, which blocks the activation of NF-κB path in the epidermal and immune cells.
