Acetylation Regulates MARK2 activity

This study investigates the interactions between two enzymes involved in regulating the protein tau’s PTMs: the kinase MARK2 and the acetyltransferase CBP. Western blot analysis revealed that CBP-mediated acetylation was increased in the absence of MARK2, indicating a possible negative feedback loop, where MARK2 is inhibiting CBP acetylation. In contrast, inactive MARK2 (MARK2-KR) was strongly acetylated in the presence of acetyl-CBP, consistent with the preferential CBP binding and targeting of the inactive MARK2 conformation. To determine the specific lysine residues in MARK2 that are subject to acetylation in the presence of CBP, we immunopurified MARK2-KR alone (as a control) and CBP-acetylated MARK2-KR. We analyzed the immunopurified MARK2-KR by mass spectrometry-based proteomics to determine differential acetyl and phosphorylation sites.