Retinoic Acid-induced Cell Cycle Arrest of Human Myeloid Cell Lines

Abstract

Retinoic acid-induced terminal differentiation of myeloid cells involves the sequential regulation of cell cycle regulatory genes, coordinating the process of differentiation with arrest in the G0/G1 phase of the cell cycle. In this review we have summarized changes in expression and activity of cell cycle regulatory proteins associated with retinoic acid induced-growth arrest in human myeloid cell lines. These changes involve: (i) an early down-regulation of c-Myc; (ii) up-regulation of p21CIP1 and p27KIP1 and, in some cases, p15INK4b or p18INK4c; (iii) down-regulation of cyclin E and cyclin D1/D3, and, at later stages, cyclin A and cyclin B; and (iv) decreased CDK activity and dephosphorylation of pRb.