The AAA ATPase p97 uses energy from ATP hydrolysis to extract or segregate ubiquitylated target proteins from stable protein assemblies, membranes and chromatin. Since p97 is involved in highly diverse cellular processes like ER associated protein degradation, autophagy and DNA repair, its activity is tightly controlled. This is achieved by a large number of regulatory cofactors and post-translational modifications including phosphorylation, ubiquitylation and sumoylation. In this project we will study the nature and dynamics of p97–cofactor interactions and their interplay with post-translational modifications in response to stress conditions known to affect pathways involving p97. Mass spectrometry and different in cellulo and in vitro techniques will be used to elucidate the physiological and patho-physiological functions of p97.