ATG16L2 - An autophagy-related protein with unknown functions

Mon, 08/10/2015 - 14:48

Autophagy is a process by which cells degrade and recycle damaged organelles or misfolded proteins. These various cargo are engulfed in a double-membrane structure called the autophagosome. The autophagosome then fuses with the lysosome to facilitate the degradation of the cargo. This process requires the concerted effort of an extensive network of proteins. One of the early steps of autophagosome assembly is the formation of the large multimeric ATG12-ATG5-ATG16 complex. This complex acts as an E3 ligase during the lipidation of ATG8. ATG8 is then incorporated into the expanding autophagosomal membrane and facilitates the recruitment of core autophagy machinery and substrates targeted for degradation. ATG16L2 is an isoform of ATG16 whose function is still unclear. While the isoform ATG16L1 is essential for autophagy, ATG16L2 does not seem to be important (1). In an examination of ATG16L2 function, Ishibashi et al. used an ATG16L2 antibody to show ubiquitous expression of ATG16L2 across a wide range of tissues. This study also performed immunoprecipitation experiments using the ATG16L2 antibody and showed ATG16L2, like ATG16, is able to form multimeric complexes with ATG12 and ATG5 (1). While ATG16L2 was able to participate in the lipidation of ATG8, ATG16L2 did not localize to the autophagosome and remained mostly cytosolic (1). These results indicate ATG16L2 does not participate directly in autophagosome formation. However a recent study of ATG16L2 did show a potential role in autophagy, specifically in T-cells (2). This study identified decreased levels of ATG16L2 using a combination of mass spectrometry and western blotting with the ATG16L2 antibody in patients with multiple sclerosis (2). This study suggests a potential role for ATG16L2 in autophagy however this role remains unknown. Monitoring of ATG16L2 levels using the ATG16L2 antibody may serve as a diagnostic tool in predicting outcomes in multiple sclerosis patients (2). A study of cell responses to cisplatin treatment used the ATG16L2 antibody as part of a panel of antibodies to monitor expression of autophagy and cell death related genes (3). The authors showed ATG16L2 levels are reduced in response to cisplatin (3). The results of this study have implications for identifying biomarkers or targets involved in tumor cell resistance to platinum based drugs (3).


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  2. 24406150
  3. 22071691

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