PHORBOL ESTER-STIMULATED CIP1 EXPRESSION IN P53-NEGATIVE LEUKEMIC-CELLS - DEATH IN THE ABSENCE OF A G(1) ARREST OR DIFFERENTIATION

In differentiating leukemic cells, cyclin-dependent kinase interacting protein (Cip1) is induced and stimulates a G(1) arrest. TPA treated U 937 monoblastoid cells expressed Cip1, hypophosphorylated retinoblasto ma protein (Rb), arrested in G(1) and differentiated. PKC-zeta cells a re U937 cells that overexpress the zeta isoform and display alteration s in endogenous PKC isoform expression. TPA treated PKC-zeta cells und ergo apoptosis without differentiating. TPA treated PKC-zeta cells exp ress Cip1 and display substantial hypophosphorylation of Rb but fail t o arrest in G(1). Thus, a novel phorbol ester dependent signalling pat hway exists in which Cip1 induction is associated with the absence of a G(1) arrest and induction of apoptosis rather than differentiation.