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Your search keyword '"Skoultchi, Arthur"' showing total 15 results
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1. Histone 1 Mutations Drive Lymphomagenesis By Inducing Primitive Stem Cell Functions and Epigenetic Instructions through Profound 3D Re-Organization of the B-Cell Genome

Author

Yusufova, Nevin, primary, Teater, Matthew R, primary, Soshnev, Alexey, primary, Kloetgen, Andreas, primary, Osunsade, Adewola, primary, Conway, Joseph, primary, Doane, Ashley, primary, Skoultchi, Arthur, primary, Tsirigos, Aristotelis, primary, David, Yael, primary, Allis, C. David, primary, Cesarman, Ethel, primary, and Melnick, Ari, primary

Published
2019
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14. Cell cycle exit during terminal erythroid differentiation is associated with accumulation of p27Kip1and inactivation of cdk2 kinase

Author

Hsieh, Fen F., Barnett, Lou Ann, Green, Wayne F., Freedman, Karen, Matushansky, Igor, Skoultchi, Arthur I., and Kelley, Linda L.

Abstract

Progression through the mammalian cell cycle is regulated by cyclins, cyclin- dependent kinases (CDKs), and cyclin-dependent kinase inhibitors (CKIs). The function of these proteins in the irreversible growth arrest associated with terminally differentiated cells is largely unknown. The function of Cip/Kip proteins p21Cip1and p27Kip1during erythropoietin-induced terminal differentiation of primary erythroblasts isolated from the spleens of mice infected with the anemia-inducing strain of Friend virus was investigated. Both p21Cip1and p27Kip1proteins were induced during erythroid differentiation, but only p27Kip1associated with the principal G1CDKs—cdk4, cdk6, and cdk2. The kinetics of binding of p27Kip1to CDK complexes was distinct in that p27Kip1associated primarily with cdk4 (and, to a lesser extent, cdk6) early in differentiation, followed by subsequent association with cdk2. Binding of p27Kip1to cdk4 had no apparent inhibitory effect on cdk4 kinase activity, whereas inhibition of cdk2 kinase activity was associated with p27Kip1binding, accumulation of hypo-phosphorylated retinoblastoma protein, and G1growth arrest. Inhibition of cdk4 kinase activity late in differentiation resulted from events other than p27Kip1binding or loss of cyclin D from the complex. The data demonstrate that p27Kip1differentially regulates the activity of cdk4 and cdk2 during terminal erythroid differentiation and suggests a switching mechanism whereby cdk4 functions to sequester p27Kip1until a specified time in differentiation when cdk2 kinase activity is targeted by p27Kip1to elicit G1growth arrest. Further, the data imply that p21Cip1may have a function independent of growth arrest during erythroid differentiation.

Published
2000
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