Institute of Structural Biology
University of Bonn

We had recently discovered a new signalling cascade in type III CRISPR immune systems, the CalpLTS cascade. In a nutshell, the CalpL protease senses cyclic oligonucleotides that are produced by the type III recognition complex, cleaves the anti-sigma factor CalpT and thereby releases the sigma factor CalpS. In our new study we have discovered that the multi functional CalpL protein also has a ring nuclease activity that degrades the cyclic oligonucleotides. It thus acts as a molecular timer that attenuates the immune response. You can read all the interesting details here....

A serial switch for kinase activation: Double-phosphorylated Cdk7 turns on full activity! The Cyclin-dependent kinase 7 has two functions, it activates other CDKs to turn on the cell cycle and it phosphorylates RNA polymerase II to initiate transcription. Robert discovered that the first function does not require Cdk7 phosphorylation whereas the second function is fully boosted by the sequential phosphorylation of two sites in the kinase T loop. Read the full story here...

Congratulations to Jan Gerhartz for his first publication of a PhD in the Nowak Lab! Jan wrote a perspective article summarizing a new concept of bifunctional small molecules that can dimerize proteins and therefore generate a more potent and selective inhibitors. Small molecule inhibition relies on maintaining high occupancy of the protein target and are frequently limited for potency and selectivity. These types of inhibitors have been recently developed to target an E3 ubiquitin ligase KEAP1. KEAP1, controlled by the redox activity of the cell is known to degrade transcription factor Nrf2. Nrf2 is known for its importance in acute inflammat...