SUMO-1-mediated Protein Degradation: SUMO-1 interacts with Transcription Factor CP2 to degrade via in Part, 26S proteasome Pathway via, in part, 26S Proteasome PathwaySUMO-1-mediated Protein Degradation: SUMO-1 interacts with Transcription Factor CP2 to degrade via, in part, 26S Proteasome PathwaySUMO-1-mediated Protein Degradation: SUMO-1 interacts with Transcription Factor CP2 to degrade via, in part, 26S Proteasome PathwaySUMO-1-mediated Protein Degradation: SUMO-1 interacts with Transcription Factor CP2 to degrade via, in part, 26S Proteasome PathwaySUMO-1-mediated Protein Degradation: SUMO-1 interacts with Transcription Factor CP2 to degrade via, in part, 26S Proteasome Pathway

초록

CP2 is a ubiquitous transcription factor that binds to and directly regulates cis-elements of various target genes, including genes controlling major cellular pathways as well as genes regulated in a tissue specific manner. Here, As an effort to understand these kinds of various regulatory mechanisms of CP2, we screened the human fetal liver cDNA library using a yeast two-hybrid assay and identified ubiquitin-conjugating enzyme 9 (Ubc9) and the small ubiquitin-like modifier-1 (SUMO-1) as ones of proteins interacting with CP2. UBC9 is a E2 conjugating enzyme to transfer SUMO-1 to target proteins, respectively, involved in post-translational modification with SUMO-1 (SUMOylation). The interactions of SUMO-1 and UBC9 with CP2 were confirmed by co-immunoprecipitation and glutathione S-transferase (GST) pull-down assays. However, despite its interaction with Ubc9 and SUMO-1, CP2 was not SUMOylated at all. Furthermore, SUMO-1 overexpression induced the suppression of transcriptional activity of CP2. Indeed, it was turned out that this transcriptional suppression was due to degradation of CP2 protein by SUMO-1. Treatment of 26S proteasome inhibitor, MG132, recovered, in part, both the cellular level of CP2 and transcriptional activity of CP2. This data indicates that 26S proteasome pathway is involved, in part, in the SUMO-1 mediated CP2 instability. Our results suggest that SUMO-1 can also mediate a novel protein degradation mechanism in vivo.