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Oncogene. 2001 Jul 19;20(32):4354-64.

P21(Cip1) induced by Raf is associated with increased Cdk4 activity in hematopoietic cells.

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Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, North Carolina, NC 27858, USA.


To investigate the functions of the different Raf genes in hematopoietic cell proliferation, the capacities of beta-estradiol-regulated Delta Raf:ER genes to induce cell cycle regulatory gene expression and cell cycle progression in FDC-P1 cells were examined. Raf activation increased the expression of Cdk2, Cdk4, cyclin A, cyclin D, cyclin E, p21(Cip1) and c-Myc and decreased the expression of p27(Kip1) which are associated with G(1) progression. However only the cell clones with moderate Raf activation, i.e. FD/Delta Raf-1:ER and FD/Delta A-Raf:ER, successfully underwent cell proliferation. The cell clones with the highest Delta Raf activity, FD/Delta B-Raf:ER, underwent apoptosis before cell proliferation. p21(Cip1) induced by Raf activation specifically bound with Cdk4/cyclin D complexes but not Cdk2/cyclin E complexes and this binding was associated with the increased Cdk4 activity. However, no binding of p27(Kip1) with either Cdk2/cyclin E or Cdk4/cyclin D was observed. Thus Raf mediated growth was associated with elevated p21(Cip1) expression, which may specifically bind with and activate Cdk4/cyclin D complexes and with decreased p27(Kip1) expression.

[Indexed for MEDLINE]

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