HMG box-containing protein 1 (HBP1) is a high mobility group (HMG) box transcription factor that negatively regulates the Wnt-beta-catenin pathway []and is involved in histone H1(0) gene expression []. It binds the transcription factor TCF4 and prevents it from binding to its target genes, including c-MYC and CYCLIN D []. It acts as a tumour suppressor and an important effector in oncogene-induced premature senescence [].
SUMO proteins are ubiquitin like proteins that are covalently attached to and detached from other proteins in cells to modify their function. SUMO is first activated in an ATP-dependent reaction by formation of a thioester bond with an E1 (SUMO-activating) enzyme and then transferred to the SUMO conjugating (E2) enzyme Ubc9. Ubc9 catalyses the formation of an isopeptide bond between the C-terminal of SUMO and the amino group of lysine in the target protein. Sumoylated proteins can be targeted for different cellular processes, such as nuclear transport, transcriptional regulation, apoptosis, and protein stability []. PIAS4 is an E3-type small ubiquitin-like modifier (SUMO) ligase, stabilising the interaction between Ubc9 and the substrate, and is a SUMO-tethering factor []. It plays a crucial role as a transcriptional coregulation in various cellular pathways, including the STAT pathway, the p53/TP53 pathway, the Wnt pathway and the steroid hormone signaling pathway. It mediates sumoylation of CEBPA, PARK7, HERC2, MYB, TCF4 and RNF168. In Wnt signaling, represses LEF1 and enhances TCF4 transcriptional activities through promoting their sumoylations [, , , , ].
