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• W2004372998 abstract "<h2>Abstract</h2><h3>Objective</h3> The aim of this study was to investigate how the tumor suppressor protein p16^INK4A interferes with growth and differentiation of leukemic U-937 cells. <h3>Materials and Methods</h3> U-937 clones constantly overexpressing the cyclin-dependent kinase inhibitor p16^INK4A were established. Clones transfected with empty vector were used as controls. The effects of high-level expression of p16^INK4A on proliferation and cell cycle progression were investigated (cell cycle distribution, proliferation rate, analyses of different cell cycle regulatory proteins). The effect of introduction of p16^INK4A on capacity for induced differentiation, assayed by capacity to reduce nitroblue tetrazolium, was determined. <h3>Results</h3> Overexpressed p16^INK4A protein was active as judged by its ability to bind to CDK-4 in a coimmunoprecipitation assay. Clones overexpressing p16^INK4A grew slower than controls, without any apparent effects on the phosphorylation status of the retinoblastoma protein (pRb). Instead, p16^INK4A overexpression affected the phosphorylation status of pRb-related pocket protein p130, which was detected in its growth-restraining hypophosphorylated form. Despite an enhanced tendency to accumulate in G₀/G₁, p16^INK4A-overexpressing cells were less sensitive to induction of differentiation with vitamin D₃ or ATRA than control cells. <h3>Conclusions</h3> Constitutive expression of p16^INK4A in U-937 cells resulted in decreased proliferation as a result of activated p130 rather than pRb. Also, we showed that introduction of p16^INK4A into U-937 cells impaired their capacity to differentiate. Moreover, the results support the notion that cell differentiation and cell cycle progression are dissociated and independently regulated processes." @default.
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• W2004372998 date "2001-12-01" @default.
• W2004372998 modified "2023-10-17" @default.
• W2004372998 title "Forced expression of the cyclin-dependent kinase inhibitor p16INK4A in leukemic U-937 cells reveals dissociation between cell cycle and differentiation" @default.
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• W2004372998 doi "https://doi.org/10.1016/s0301-472x(01)00743-3" @default.
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