CSNK1A1 Human
Description
Biological Functions
CSNK1A1 regulates multiple signaling pathways:
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Wnt/β-catenin: Phosphorylates β-catenin at Ser45, marking it for degradation
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p53 Regulation: Inhibits p53 by promoting MDM2 activity; loss of CSNK1A1 stabilizes p53, inducing apoptosis
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Cell Cycle: Essential for mitotic spindle formation and centrosome function
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Apoptosis: Anti-apoptotic in TRAIL/Fas pathways by phosphorylating BID and DISC components
Clinical Implications
Disease Associations
Pharmacological Targeting
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Degraders: SJ3149 (oral bioavailability: 12%; IP bioavailability: 74%) induces CK1α degradation in vivo (IC₅₀: 12.59 μM)
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Inhibitors: D4476 reduces leukemia stem cell viability by 80% vs. 20% in normal hematopoietic cells
Research Applications
Recombinant CSNK1A1 (ProSpec Bio)
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Formulation: 0.5 mg/mL in Tris-HCl (pH 8.0), 0.4M urea, 10% glycerol
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Stability: Store at -20°C with carrier protein (e.g., 0.1% HSA)
Experimental Findings
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CRISPR knockout of CSNK1A1 in MOLM-13 AML cells reduced viability by 15–40-fold
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High CSNK1A1 mRNA correlates with shorter survival in AML (HR: 2.1; p < 0.001)
Future Directions
Current research focuses on:
Product Specs
Product Science Overview
Casein Kinase 1 Alpha 1 (CK1α1) is a serine/threonine protein kinase that belongs to the Casein Kinase 1 (CK1) family. This enzyme is encoded by the CSNK1A1 gene in humans and is involved in various cellular processes, including membrane trafficking, cell cycle progression, chromosome segregation, apoptosis, autophagy, cell metabolism, differentiation, circadian rhythm, immune response, neurodegeneration, and cancer .
CK1α1 is expressed as four alternatively spliced transcript variants, resulting in four protein isoforms of varying lengths. These isoforms mainly differ by the presence or absence of a 28-amino acid “L” insert in the kinase domain and a 12-amino acid “S” insert near the C terminus . The recombinant form of CK1α1 is often produced using baculovirus expression systems in insect cells, with an N-terminal GST tag for purification and stability .
CK1α1 plays a crucial role in several signaling pathways, most notably the Wnt/β-catenin signaling pathway. It phosphorylates β-catenin at Ser45, which is part of the β-catenin destruction complex, leading to β-transducin repeat-containing E3 ubiquitin protein ligase (β-TrCP)-mediated ubiquitination and proteasomal degradation . Additionally, CK1α1 targets the tumor suppressor protein p53 for degradation, mediated by murine double minute clone 2 (MDM2) and MDM4 (also known as MDMX), while stabilizing and positively regulating the transcription factor E2F-1, which is involved in cell cycle progression .
CK1α1 is a promising therapeutic target due to its involvement in diverse cellular, physiological, and pathological processes. For instance, lenalidomide, a thalidomide analog, is an effective treatment for myelodysplastic syndrome with deletion of chromosome 5q [MDS del (5q)], exerting its effects by inducing CK1α1 ubiquitination and degradation . This suggests that CSNK1A1 is a conditionally essential malignancy gene and a potential target for anti-cancer drugs .
Recombinant human CK1α1 is produced using baculovirus expression systems in insect cells, with an N-terminal GST tag for purification and stability . The recombinant protein is used in various research applications, including studies on cell signaling, cancer research, and drug development. It is supplied in a sterile buffer and should be stored at –70°C to maintain its stability and activity .
