Research Report 2010 - MDC

Graduate StudentsKatrin BagolaHolger BrendebachSabine HornLaura JänickeMartin MehnertMarcel NowakFranziska ZimmermannTechnical AssistantsCorinna VolkweinAngelika WittstruckSecretariatSylvia KlahnFigure 1. ER-associated protein degradation in yeast and mammalian cells.Molecular chaperones and proteins of the glycosylhydrolase-47 family (Mns1 andHtm1) detect misfolded polypeptides and direct them to membrane bound ligases(Doa10, RMA1, HRD). After dislocation to the cytosolic face of the ER membrane,substrates are ubiquitylated by an ubiquitin ligase. All ligase complexes comprise acentral, catalytic active RING finger protein (E3), ubiquitin-conjugating enzymes(E2), and additional factors. The AAA ATPase Cdc48 releases ubiquitylated moleculesfrom the ER membrane. The adapter proteins Rad23 and Dsk2 escort the ubiquitylatedsubstrates to the 26S proteasome for degradation. Concurrently Png1 deglycosylatesglycoproteins through its association with Rad23. Proteins containing a glycan-interactionmotif or ubiquitin-binding domains are depicted in red and blue,respectively. Proteins are labeled with their yeast names in blue and green lettersindicate the mammalian counterpart.Cancer Research 103