SETD7 promotes LC3B methylation and degradation in ovarian cancer.

Microtubule-associated protein 1 light chain 3 (LC3) is a key autophagy-related protein involved in regulating autophagosome formation and autophagy activity. Post-translational modifications of LC3 are necessary to modulate its function. However, LC3 protein methylation and its physiological significance have not yet been elucidated. Here, we show that SET domain containing lysine methyltransferase 7 (SETD7) interacts with LC3B, a common isoform of LC3, and methylates LC3B at lysine 51 (K51). SETD7-mediated methylation of LC3B promotes ubiquitination and degradation of LC3B, resulting in reduced autophagosome formation. Furthermore, SETD7 exerts a tumor-promotive function in ovarian cancer (OC) cells in a K51 methylation-dependent manner. Collectively, our data define a novel modification of LC3B and highlight the oncogenic effect of SETD7 via mediating LC3B methylation and degradation.