The CCNY Knockout K-562 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population in which the CCNY gene encoding Cyclin Y has been disrupted. This heterogeneous pool of gene-edited K-562 cells provides a loss-of-function model suitable for studying CCNY-dependent signaling pathways without the bias of clonal selection. The polyclonal format allows researchers to analyze CCNY deficiency across a diverse spectrum of genetic edits, more closely representing the variability inherent in cellular populations.
K-562 is a suspension-adapted lymphoblast cell line derived from the pleural effusion of a 53-year-old female with chronic myeloid leukemia in blast crisis. These BCR-ABL positive, p53-null cells retain characteristics of multipotent hematopoietic progenitors capable of commitment to erythroid, granulocytic, and monocytic lineages. The cell line is widely used as a model for CML, hematopoiesis, and signal transduction research, offering a well-characterized genetic background and adaptability to high-throughput applications.
CCNY partners with CDK14 to phosphorylate the Wnt co-receptor LRP6, potentiating ??-catenin stabilization. Upstream WNT3A, along with PKA and E2F transcription factors, regulate this process. LRP6 phosphorylation recruits DVL, inhibiting the AXIN destruction complex, and permitting ??-catenin nuclear translocation to activate TCF/LEF target genes MYC and CCND1, thereby driving G2/M cell cycle progression. This positions CCNY as a critical link between Wnt reception and cell cycle machinery.
In K-562 leukemia cells, oncogenic BCR-ABL signaling may cooperate with Wnt/??-catenin activity to support leukemic proliferation. CCNY-mediated LRP6 phosphorylation likely amplifies this pathway, contributing to the maintenance of leukemic stem cell properties. Disruption of CCNY is expected to attenuate LRP6 phosphorylation, diminish ??-catenin activity, and impair expression of proliferation-associated genes, offering a means to dissect the relative contributions of BCR-ABL and Wnt signaling in CML pathogenesis and to evaluate CCNY as a therapeutic target.
Applications include Wnt pathway analysis using phospho-LRP6 western blotting, ??-catenin reporter assays (TOPFlash/FOPFlash), and RT-qPCR of MYC or CCND1. Cell cycle profiling by flow cytometry, co-immunoprecipitation of CDK14, and colony formation assays enable functional characterization. The cells are also suited for drug sensitivity screens and functional genomics studies in leukemia research. For further information, please contact Ascent Research.
