ENHANCED CELL-DIFFERENTIATION WHEN RB IS HYPOPHOSPHORYLATED AND DOWN-REGULATED BY RADICICOL, A SRC-KINASE INHIBITOR

Radicicol, an inhibitor of src or are-like kinases, causes hypophospho rylation and down-regulation of the RB retinoblastoma tumor suppressor protein in HL-60 human promyelocytic leukemia cells. Both of these ch anges in the RB protein typically are associated with myeloid or monoc ytic differentiation of these cells induced by retinoic acid or 1,25-d ihydroxy vitamin D3. When added with either inducer, radicicol caused the typically induced myeloid or monocytic differentiation of these ce lls to be accelerated. By itself radicicol caused a transient inhibiti on of G1 to S transit, but did not cause phenotypic conversion. The do wn-regulation and dephosphorylation of RB by radicicol may thus facili tate cell differentiation. (C) 1994 Academic Press, Inc.