5q32

CK1,CK1a,CKIa,HEL-S-77p,HLCDGP1,PRO2975

Cell cycle control

CK1 alpha phosphorylates the tumor suppressor p53 although it seems as if CK1 delta is the most important kinase in the regulation of p53 activity and interacts with several cellular proteins including the oncoprotein Mdm2.

Apoptosis

Recently is has been shown, that CK1 is involved in negatively regulating apoptosis through phosphorylation of diverse cellular proteins including the p75 tumor necrosis factor, proteins of the death-inducing signaling complex (TRAIL induced apoptosis) or Bid (FAS-mediated apoptosis).
It is thought, that CK1 mediated phosphorylation at the level of death-inducing signaling complex (DISC) leads to resistance against caspase cleavage and thereby down regulation of TRAIL (tumor necrosis-factor-related apoptosis ligand) induced apoptosis.
Furthermore, there is evidence that CK1 alpha regulates Fas-mediated apoptosis through phosphorylation of the proapoptotic Bcl2 family member Bid, which prevents caspase 8-dependant cleavage of Bid and negatively influences Fas response.
Additionally, evidence has increased that CK1 alpha modulates RXR agonist mediated apoptosis through interaction and/or phosphorylation of RXR, which prevents cytochrome C realease from the mitochondria.

The Wnt pathway is a complex signaling cascade regulating cell proliferation and differentiation. During recent years, the significance of Wnt signaling in human cancer has been elucidated. Identification of numerous pathway components and mutations in the encoding genes finally result in stabilization and accumulation of beta-Catenin and enhanced transcription of TCF/LEF- beta-Catenin target genes.
CK1 alpha is part of the beta-Catenin destruction complex where it phosphorylates beta-Catenin at Serin 45, priming the subsequent phosphorylation of beta-Catenin by GSK3 beta. These phosphorylations mark beta-Catenin for proteasomal degradation. This is one of the central regulatory events controling the Wnt signaling-pathway.
Furthermore, CK1 has been shown to additionally regulate Wnt-signaling through phosphorylation of diverse cellular proteins including LEF-1 (lymphocyte enhancer factor-1) and beta-Catenin leading to the disruption of the LEF-1/ beta-Catenin transcription complex.
For additional information about Wnt-signaling in general, Wnt-signaling components and Wnt target genes, readers are referred to the Wnt-Homepage posted by the Nusse group.

Neurodegenerative disorders

Deregulation of CK1 expression and activity has been linked to various diseases including neurodegenerative disorders, especially in tauophathies like Alzheimers and Parkinsons disease.