Ubiquitination Isn’t Just for Recycling Anymore
Ubiquitin is a small protein, which can be attached to other cellular proteins - a post-translational modification called ubiquitination. Discoveries in the ’80s illuminated ubiquitin as a label for degradation and recycling of the modified protein. Recent studies however, are suggesting more nuanced roles for ubiquitin in signal transduction and cellular function.
A study headed by the Junior Group of Dr. Daniel Krappmann (GSF - National Research Center for Environment and Health, Institute of Toxicology) in collaboration with Dr. Jürgen Ruland (TU Munich) and Dr. Claus Scheidereit (Max-Delbrück-Center, Berlin) has uncovered a vital role for ubiquitination (and de-ubiquitination) in the adaptive immune response. Upon specific recognition of antigens presented on the surface of antigen-presenting cells by T cells, biochemical signals are initiated that lead to a concerted response by the immune system against invading pathogens. The participants (see figure) of this biochemical signaling process were known, but one of the steps involves an activation of IkB kinase (IKK) by the Carma1-Bcl10-Malt1 (CBM) complex, and it was unknown how.
‘Mechanistically, ubiquitin is virtually acting as all-purpose glue that links different protein components inside the cell’, Krappmann explains. ’However, ubiquitination provides an important advantage compared to conventional adhesives: It is reversible, meaning that the associations can be resolved’.
The paper in question by Oeckinghaus et al. (2007) uses Western Blotting, immunoprecipitation, and related data extremely heavily, which is a boring and unattractive way to present data to a non-molecular biologist. But it gets the point across - that ubiquitination is necessary for CBM-IKK interaction, and not just as a trash label.
- Oeckinghaus, A., Wegener, E, Welteke, V., Ferch, U., Çöl Arslan, S., Ruland, J., Scheidereit, C. and Krappmann, D. (2007) Malt1 ubiquitination triggers IKK/NF-?B signalling upon T cell activation. EMBO J.; [Ahead of print, 18th of Oct. 2007]; doi: 10.1038/sj.emboj.7601897
molecular biology
