Growing sphere of influence: Cdc48/p97 orchestrates ubiquitin-dependent extraction from chromatin.

The AAA (ATPases associated with various cellular activities) family member Cdc48/p97 is best known for its role in ubiquitin-dependent proteasomal degradation of aberrant endoplasmic reticulum (ER) proteins, a process known as ER-associated degradation (ERAD). However, recent studies have also defined Cdc48/p97 as a central player in various chromatin-associated processes linked to cell cycle progression, DNA replication, transcription, and the DNA damage response. Notwithstanding the apparent differences in location and function, the role of Cdc48/p97 in ubiquitin-dependent extraction from chromatin (UDEC) bears striking similarities with its action in ERAD. Here, we discuss recent data that expand our current model of the role of Cdc48/p97 as a ubiquitin-selective segregase in the nuclear chromatin environment.