The TrkA receptor tyrosine kinase is crucial for differentiation and survival of nerve-growth-factor-dependent neurons. Paradoxically, TrkA also induces cell death in pediatric tumor cells of neural origin, via an unknown mechanism. Here, we show that CCM2, a gene product associated with cerebral cavernous malformations, interacts with the juxtamembrane region of TrkA via its phosphotyrosine bi...

Stalled replication forks are a critical problem for the cell because they can lead to complex genome rearrangements that underlie cell death and disease. Processes such as DNA damage tolerance and replication fork reversal protect stalled forks from these events. A central mediator of these DNA damage responses in humans is the Rad5-related DNA translocase, HLTF. Here, we present biochemical a...

Picsel is an information integration system 1 over sources that are distributed and possibly heterogeneous. The approach which has been chosen in Picsel is to deene an information server as a knowledge-based mediator in which Carin is used as the core logical formalism to represent both the domain of application and the contents of information sources relevant to that domain. In this paper, we ...

The transcription initiation and elongation steps of protein-coding genes usually rely on unrelated protein complexes. However, the TFIIS elongation factor is implicated in both processes. We found that, in the absence of the Med31 Mediator subunit, yeast cells required the TFIIS polymerase II (Pol II)-binding domain but not its RNA cleavage stimulatory activity that is associated with its elon...

The discovery of retigabine has provided access to alternative anticonvulsant compounds with a novel mode of action. Acting as potassium channel opener, retigabine exclusively activates neuronal KCNQ-type K(+) channels, mainly by shifting the voltage-dependence of channel activation to hyperpolarizing potentials. So far, only parts of the retigabine-binding site have been described, including T...