CSNK1D Human
Description
Molecular Characterization of CSNK1D
CSNK1D (casein kinase 1 delta) is a serine/threonine-protein kinase encoded by the CSNK1D gene located on human chromosome 17q25 . It belongs to the CK1 family, which regulates diverse cellular processes, including circadian rhythms, Wnt/β-catenin signaling, DNA repair, and apoptosis . The protein comprises 415–428 amino acids, depending on transcription variant (TV), with three major isoforms (TV1, TV2, TV3) differing in C-terminal sequences .
| Transcription Variant | Length (Amino Acids) | Key Features |
|---|---|---|
| TV1 | 415 | Canonical isoform; high autophosphorylation |
| TV2 | 409 | Reduced kinase activity compared to TV1 |
| TV3 | 427 | Enhanced substrate phosphorylation efficiency |
Kinetic studies reveal TV3 exhibits superior catalytic activity for substrates like β-catenin .
Biological Roles and Pathways
CSNK1D integrates into multiple signaling networks:
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Wnt/β-catenin: Phosphorylates DVL2/3 and β-catenin, modulating cell proliferation .
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Circadian Rhythms: Phosphorylates PER1/2, stabilizing the circadian clock .
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DNA Damage Response: Interacts with p53 and TOP2A to regulate repair mechanisms .
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Immune Modulation: Correlates with immune cell infiltration (e.g., macrophages, neutrophils) in tumors .
Prognostic Biomarker
Elevated CSNK1D expression is linked to poor survival in hepatocellular carcinoma (HCC), breast cancer (BRCA), and colorectal cancer (COAD) :
| Cancer Type | Hazard Ratio (OS) | P-value |
|---|---|---|
| HCC | 2.14 | <0.001 |
| BRCA | 1.67 | 0.003 |
| COAD | 1.89 | 0.001 |
In TCGA data, CSNK1D overexpression in HCC correlates with advanced pathological stage (p<0.01) and metastasis .
Functional Impact in Tumorigenesis
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Proliferation: Knockdown reduces HCC and breast cancer cell viability by 40–60% (CCK-8 assays) .
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Metastasis: Silencing CSNK1D in MDA-MB-231 cells decreases invasion by 70% (Transwell assays) .
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Immune Evasion: High CSNK1D expression associates with increased PD-L1 and CTLA-4 levels in tumors .
Oncological Applications
Preclinical studies highlight CSNK1D inhibition as a strategy to counteract tumor progression:
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Small-Molecule Inhibitors: Reduce lung metastasis in breast cancer xenografts by 50% .
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Immunotherapy Synergy: High CSNK1D levels correlate with tumor mutation burden (TMB) and microsatellite instability (MSI), suggesting responsiveness to checkpoint inhibitors .
Non-Cancer Roles
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Circadian Disorders: Mutations in CSNK1D are implicated in familial advanced sleep phase syndrome (FASPS2) .
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Infectious Diseases: Parasitic CK1 homologs (e.g., Plasmodium) hijack host CK1δ pathways, suggesting cross-species targeting opportunities .
Research Gaps and Future Directions
Product Specs
Product Science Overview
CK1δ is one of several isoforms within the CK1 family, which also includes CK1α, CK1γ1, CK1γ2, CK1γ3, and CK1ε . These isoforms share a high degree of homology in their catalytic domains but differ in their N-terminal and C-terminal non-catalytic domains . The molecular weight of CK1 isoforms ranges from 37 kD (CK1α) to 51 kD (CK1γ3) .
CK1δ is involved in multiple cellular functions:
- Cell Proliferation and DNA Damage Response: CK1δ regulates cell proliferation and is involved in the DNA damage response .
- Circadian Rhythm: CK1δ plays a significant role in the regulation of circadian rhythms by phosphorylating key proteins involved in the circadian clock .
- Tumorigenesis: CK1δ has been implicated in cancer-related signaling pathways, such as Wnt/β-catenin, PI3K/AKT, and Hedgehog . It is genetically amplified in a portion of human epithelial ovarian cancer (EOC) .
