PTK2-mediated degradation of ATG3 impedes cancer cells susceptible to DNA damage treatment.

ABSTRACT: ATG3 (autophagy-related 3) is an E2-like enzyme essential for autophagy; however, it is unknown whether it has an autophagy-independent function. Here, we report that ATG3 is a relatively stable protein in unstressed cells, but it is degraded in response to DNA-damaging agents such as etoposide or cisplatin. With mass spectrometry and a mutagenesis assay, phosphorylation of tyrosine 203 of ATG3 was identified to be a critical modification for its degradation, which was further confirmed by manipulating ATG3^Y203E (phosphorylation mimic) or ATG3^Y203F (phosphorylation-incompetent) in Atg3 knockout MEFs. In addition, by using a generated phospho-specific antibody we showed that phosphorylation of Y203 significantly increased upon etoposide treatment. With a specific inhib

SUBMITTER: Ma K 

PROVIDER: S-EPMC5361600 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature