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

Abstract

Casein kinase 1δ (CK1δ) 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 CK1δ is targeted by the ubiquitin ligase APC/CCdh1 is not understood how CK1δ expression is regulated to support its multiple functions. Here, we show that kinase activity controls CK1δ homeostasis by coordinating two competing processes: export from the nucleus to ensure distribution of CK1δ between its assembly partners, and proteasomal degradation of unassembled CK1δ in the nucleus to keep the amount of active, potentially deleterious orphan kinase low. During mitosis, CK1δ is released from centrosomes and stabilized by (auto)phosphorylation to preserve it for the subsequent G1 phase.