RUBCNL (F3S8R) Rabbit Monoclonal Antibody #26461

Rubicon-like autophagy enhancer (RUBCNL), also known as PACER, C13orf18, and KIAA0226L, is a key multifunctional enhancer in autophagy. By antagonizing Rubicon, a known negative regulator of autophagy, RUBCNL stimulates the activity of the PI3K/PI3KC3 complex, which is essential for autophagosome formation and maturation. RUBCNL also acts as a positive regulator of autophagosome maturation by localizing to autophagic structures and promoting the biogenesis of phosphatidylinositol 3-phosphate, a key lipid required for autophagy. Additionally, following its anchorage to the autophagosomal SNARE protein STX17, RUBCNL facilitates the recruitment of PI3K/PI3KC3 and HOPS complexes to the autophagosome (1). RUBCNL has also been shown to function as a negative regulator of both RIPK1-dependent apoptosis and necroptosis by forming a complex with RIPK1 and limiting the assembly of the RIPK1-TNFRSF1A/TNFR1 complex I. This suggests a dual functionality of RUBCNL in both autophagy and regulated cell death pathways (2).Under nutrient-rich conditions, RUBCNL is negatively regulated by mTORC1 phosphorylation, which disrupts the association of RUBCNL with STX17 and the HOPS complex. Under starvation conditions, RUBCNL is dephosphorylated, which facilitates its acetylation by the activated GSK3-KAT5/TIP60 pathway and significantly enhances HOPS complex recruitment, autophagosome maturation, and lipid metabolism. Moreover, hepatocyte-specific RUBCNL knockout in mice resulted in impaired autophagy flux, glycogen and lipid accumulation, and liver fibrosis (3,4).Elevated tumor-derived lactate levels can increase RUBCNL expression through histone lactylation, which facilitates autophagosome maturation, promotes hypoxic cancer cell proliferation and survival, and leads to resistance to bevacizumab treatment in colorectal cancer (5). RUBCNL function perturbation and the autophagy process can also lead to the accumulation of SOD1 aggregates and motoneuron cell death in ALS models (6). RUBCNL has been shown to positively regulate the therapeutic potential of mesenchymal stem cells (MSC) in a mouse model of colitis, suggesting that augmentation of autophagic capacity in MSC by increasing RUBCNL levels may have therapeutic implications for inflammatory bowel disease (7).