Characterizing the Novel Interaction Between Human Ubiquitin Specific Protease 7 (USP7) and Forkhead Box M1 (FOXM1)

Ubiquitin Specific Protease 7 (USP7) is a deubiquitinase that cleaves ubiquitin from substrate protein(s) in order to alter their stability, localization or activity. USP7 is essential as it regulates the stability of many proteins involved in various cellular pathways. USP7 utilises the 164DWGF167 motif found in the TRAF domain at the NTD of USP7 to interact with substrates containing P/A/ExxS motifs. Many P/A/ExxS motifs were identified in Forkhead Box M1 (FOXM1), a transcription factor whose expression is exclusively found in cells that are actively proliferating, and is responsible for activating transcription of genes needed for cell cycle progression. Pull-down assays demonstrated that USP7 and FOXM1 interact in vivo, and in vitro. FOXM1 levels were shown to vary depending on the amount of USP7 present in vivo, indicating that USP7 regulates FOXM1 stability. As a result, FOXM1 has been identified as a novel interacting partner of USP7.