CK1δ homeostasis by activity-dependent shuttling and degradation of orphan kinase

Casein kinase 1{delta} (CK1{delta}) is a simple monomeric enzyme involved in the regulation of a variety of functions, including signal transduction, the circadian clock, and the cell cycle. Although CK1{delta} is targeted by the ubiquitin ligase APC/CCdh1 is not understood how CK1{delta} expression is regulated to support its multiple functions. Here, we show that kinase activity controls CK1{delta} homeostasis by coordinating two competing processes: export from the nucleus to ensure distribution of CK1{delta} between its assembly partners, and proteasomal degradation of unassembled CK1{delta} in the nucleus to keep the amount of active, potentially deleterious orphan kinase low. During mitosis, CK1{delta} is released from centrosomes and stabilized by (auto)phosphorylation to preserve it for the subsequent G1 phase. TeaserCompetitive nuclear export and nuclear degradation of active CK1{delta} ensure efficient partner interaction and keep unassembled kinase levels low.