Domain protecting proteins from degradation identified
Apr 18, 2005 - 9:36:38 PM

The first stabilizing signal that protects a protein from degradation has been identified.

Dr Nico Dantuma’s research group at Karolinska Institutet has identified the first cellular stabilization signal, which protects a protein from being degraded.

Rad23 is a protein that is important for DNA repair and protein degradation and for both functions, it has to bind to the proteasome (see below). The new findings show that a motif in the tail of Rad23, the so called UBA domain, protects it from degradation. Interestingly, it has been described that Rad23 is itself linked to the proteasome but it is not degraded by the proteasome. Because of this stabilization signal, Rad23 is the perfect shuttle to bring things to the proteasome since it can escape every time and be reused over and over again. UBA domains from several other proteins can also protect proteins from degradation showing that it is a general phenomenon.

The ubiquitin/proteasome system:
Proteins that have to be degraded in the cell are labelled through the linkage of a chain of many ubiquitins, which is a small abundant protein. This chain of ubiquitins binds to the proteasome, which is a large barrel shaped protease complex. The proteasome starts to unravel the protein that has to be degraded and transports it into the belly of the proteasome, where the protein is chopped in small pieces. It is well established that proteins, that have to be labelled with ubiquitin and next degraded by the proteasome, are recognized by the presence of ’degradation signals’, which are recognition motives within proteins that triggers enzymes to link a ubiquitin chain to this protein.

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