Malt1 ubiquitination triggers NF-kB signaling upon T-cell activation.

Triggering of antigen receptors on lymphocytes is critical for initiating adaptive immune response against pathogens. T-cell receptor (TCR) engagement induces the formation of the Carma1-Bcl10-Malt1 (CBM) complex that is essential for activation of the IkB kinase (IKK)/NF-kB pathway. However, the molecular mechanisms that link CBM complex formation to IKK activation remain unclear. Here we report that Malt1 is polyubiquitinated upon T-cell activation. Ubiquitin chains on Malt1 provide a docking surface for the recruitment of the IKK regulatory subunit NEMO/IKKgamma. TRAF6 associates with Malt1 in response to T-cell activation and can function as an E3 ligase for Malt1 in vitro and in vivo, mediating lysine 63-linked ubiquitination of Malt1. Multiple lysine residues in the C-terminus of Malt1 serve as acceptor sites for the assembly of polyubiquitin chains. Malt1 mutants that lack C-terminal ubiquitin acceptor lysines are impaired in rescuing NF-kB signaling and IL-2 production in Malt1-/- T cells. Thus, our data demonstrate that induced Malt1 ubiquitination is critical for the engagement of CBM and IKK complexes, thereby directing TCR signals to the canonical NF-kB pathway

Stabilität und Staatsschulden: die europäische Wirtschaftspolitik in der strategischen Sackgasse

While single elements of the European economic policy design are well founded, and have developed with some politico-economic logic from the history of stabilization policy, a coherent "concept" of monetary and fiscal policy is lacking. There is no agent who is responsible for demand stabilization on the European level. As a consequence, the Stability and Growth Pact is unlikely to survive unless the national budgets are sheltered from EMU recessions by monetary policy. The ECB ought to show responsibility also for output stabilization. Alternative reforms, global fiscal demand policies or structural policies are less advisable. Obwohl einzelne Elemente der europäischen Wirtschaftspolitik theoretisch wohl begründet sind und an der vorangegangenen Geschichte der Stabilitätspolitik im EWS anknüpfen, fehlt ein kohärentes Gesamtkonzept. Die Rolle eines für Nachfrage- und Konjunkturpolitik auf EWU-Ebene zuständigen Akteurs ist nicht besetzt. Dies ist auch der Grund für die Krise des Stabilitäts- und Wachstumspaktes. Er kann als ein sinnvolles Disziplinierungsinstrument nur überleben, wenn die nationalen Budgets durch eine aktive Geldpolitik vor den Folgen europäischer Konjunkturkrisen geschützt werden. Die Europäische Zentralbank sollte eine Verantwortung für die Outputstabilisierung übernehmen. Andere Auswege aus dem gegenwärtigen Dilemma - eine Nachfragesteuerung durch koordinierte Fiskalpolitik oder eine Intensivierung der Strukturpolitik - sind weniger empfehlenswert.

Time-Varying Fundamentals of the Euro-Dollar Exchange Rate

This study examines changes in the impact of the economic fundamentals on the euro-dollar exchange rate. First, the monetary model is augmented with the equity markets and the model is estimated in its structural form. Second, the time-varying impacts of the long-run fundamentals representing equilibrium in different markets on the euro-dollar exchange rate are examined using Kalman filtering. The time-varying structural model indicated that the relative importance of the different fundamentals was not equal and the impact of the fundamentals was time-dependent.Exchange rate, euro-dollar, structural form, Kalman filtering,

NF-κB signaling pathways regulated by CARMA family of scaffold proteins

The NF-κB family of transcription factors plays a crucial role in cell activation, survival and proliferation. Its aberrant activity results in cancer, immunodeficiency or autoimmune disorders. Over the past two decades, tremendous progress has been made in our understanding of the signals that regulate NF-κB activation, especially how scaffold proteins link different receptors to the NF-κB-activating complex, the IκB kinase complex. The growing number of these scaffolds underscores the complexity of the signaling networks in different cell types. In this review, we discuss the role of scaffold molecules in signaling cascades induced by stimulation of antigen receptors, G-protein-coupled receptors and C-type Lectin receptors, resulting in NF-κB activation. Especially, we focus on the family of Caspase recruitment domain (CARD)-containing proteins known as CARMA and their function in activation of NF-κB, as well as the link of these scaffolds to the development of various neoplastic diseases through regulation of NF-κB