The AMPK kinase Sak1 activates separase and promotes its nuclear localization during mitosis.

Sak1 kinase activates and promotes nuclear localization of separase during mitosis in Saccharomyces cerevisiae, with conservation in humans involving LKB1.

• Why it matters: Proper chromosome segregation depends on tightly regulated separase activity, and understanding its regulation could reveal mechanisms underlying mitotic fidelity and potential links to cancer.
• What they did: Researchers identified Sak1 as a novel separase regulator through a suppressor screen, showing Sak1 phosphorylates separase independently of Snf1, enhancing its activity and nuclear localization, and demonstrated physical association between human separase and LKB1.
• The result: Loss of Sak1 delays Cdc14 activation and mimics FEAR pathway defects, suggesting Sak1’s role in mitosis, and the conserved interaction with LKB1 indicates a fundamental kinase-protease regulatory mechanism across species.