UBE4B (F4F3K) Rabbit mAb #17673

Ubiquitination Factor E4B (UBE4B) is a mammalian homolog of the S. cerevisiae protein UFD2 and the first identified E4 ubiquitination factor (1). As a component of the ubiquitin-proteasome system (UPS), UBE4B functions as both an E3 and E4 ubiquitin ligase and is involved in various cellular processes, including DNA damage response, cell cycle regulation, protein quality control, and signal transduction. Its key role includes facilitating the polyubiquitination of specific substrates, most notably the tumor suppressor p53, thereby promoting its MDM2-mediated proteasomal degradation (2). Overexpression or gene amplification of UBE4B has been observed in brain tumors, breast cancer, and hepatocellular carcinoma, where inhibition of p53 leads to decreased apoptosis and increased tumor cell survival (3-5). Recent studies have shown that UBE4B phosphorylation through ATR signaling reduces its binding affinity to p53, whereas dephosphorylation by Wip1 plays a crucial role in stabilizing the activity of UBE4B in response to DNA damage (6). UBE4B also plays a role in neuronal survival and death regulation, and is associated with pathways independent of the p53 family, such as polyglutamine aggregation and Wallerian degeneration (7). It is involved in the polyubiquitination of abnormal proteins that accumulate in neurodegenerative diseases, such as ataxin-3 in Machado-Joseph disease (8), and regulates APP ubiquitination and trafficking, impacting the generation of amyloid β in Alzheimer's disease plaques (9). Additionally, UBE4B enables cytosolic-mitochondrial communication of cellular stress via its translocation to mitochondria and elongation of ubiquitin chains on mitofusin, leading to mitochondrial fragmentation (10).