Like apoptosis, autophagy is a highly regulated physiologic process that involves cellular degradation and recycling of organelles and macromolecules. Autophagy is a survival mechanism induced by states of stress, starvation, and infection. A double membraned autophagosome sequesters the desired cellular components before fusing with a lysosome to form an autolysosome destined for degradation. LC3 lipidation and recruitment to the autophagosome is crucial to its maturation and eventual fusion with a lysosome. ATG16L1 (autophagy-related protein 16-1) forms a highly conserved complex with ATG5 and ATG12 to direct LC3 to the autophagosome (1). ATG16L1 is a 68 kDa protein that exists in the cytoplasm and is directed to the preautophagosomal structure (PAS) as needed. ATG16L1 interacts with NOD1 and NOD2 in anti-bacterial autophagy to direct autophagosome formation and localization to the site of bacterial invasion (2). ATG16L1 also modulates the NOD1/NOD2 inflammatory response by blocking Rip2 recruitment and preventing NFκB and MAPK pro-inflammatory signaling. Polymorphisms in ATG16L1 have been linked to Crohn’s disease and Inflammatory Bowel disease.
Plantinga et. al. used the ATG16L1 antibody to understand how the T300A polymorphism contributed to the cytokine response seen in Crohn’s disease (3). The group used the ATG16L1 antibody to assess expression levels in their wild type (300 Ala/Ala) and mutant (300 Thr/Thr) cells. The ATG16L1 antibody showed decreased ATG16L1 expression in the mutant cells, suggesting that the polymorphism impairs normal expression levels. The group also demonstrated that the mutant cells had elevated levels of IL-1β and IL-6 during NOD2 stimulation, suggesting a mechanism for the inflammatory response seen in Crohn’s disease patients with the T300A polymorphism.
Autophagy dysregulation has also been identified in a number of malignancies. Tang et. al. sought to determine if ATG16L1 could be used as a prognostic factor for oral squamous cell carcinoma (OSCC) (4). The group used the ATG16L1 antibody to stain 90 OSCC patient samples. Intense staining with the ATG16L1 antibody correlated with advanced stage tumors and metastases. The group suggests that ATG16L1 expression should be used as a prognostic biomarker for identifying more aggressive phenotypes in OSCC patients.
Novus Biologicals offers ATG16L1 reagents for your research needs including:
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