CK1δ 的细胞周期偶联周转、自抑制与活性
Cell cycle-coupled CK1δ turnover, autoinhibition, and activity
CK1δ 的活性与丰度受细胞周期协同调控：G1 期组装的 CK1δ 激酶稳定，而游离的活性激酶被降解；S 期未组装的 CK1δ 似乎不再被降解，可能支持 DNA 损伤信号传导功能。进入有丝分裂时，磷酸酶下调促进 CK1δ 的（自）磷酸化并导致自抑制，从而保留激酶池以快速重建分裂后的稳态。此前研究已显示 CK1δ 受激酶活性、亚细胞定位及与 PER2 等结合伙伴相互作用的影响而动态调控，本研究进一步揭示其周转与细胞周期偶联。
来源：eLife · doi.org
Casein kinase 1δ (CK1δ) is a ubiquitously expressed kinase involved in diverse cellular processes, including cell-cycle regulation. CK1δ activity is attenuated by (auto)phosphorylation. However, inhibitory phosphorylation is efficiently opposed by cellular phosphatases as CK1δ accumulates in its hypophosphorylated, active state. CK1δ is a target of the nuclear ubiquitin ligase APC/C-CDH1, yet the kinase is apparently stable. Thus, the physiological relevance of CK1δ (auto)phosphorylation, autoinhibition, and regulated turnover has remained unclear. Previously, we showed that CK1δ is dynamically regulated in a manner that is dependent on kinase activity, subcellular localization, and interaction with its binding partners, such as PER2 (Serrano et al., 2026). Here, we show that CK1δ activity and abundance are additionally coordinated in a cell cycle-dependent manner. During G1, assembled CK1δ kinase is stable while free active kinase is degraded. In S phase, unassembled CK1δ seems to be no longer degraded, likely to support functions in DNA damage signaling. Upon mitotic entry, the downregulation of phosphatases promotes CK1δ (auto)phosphorylation and consequent autoinhibition, thereby preserving a pool of kinase to rapidly re-establish the post-mitotic steady state.