C-Myc regulates the CDK1/cyclin B1 dependent‑G2/M cell cycle progression by histone H4 acetylation in Raji cells.

Abstract

Overexpression of c-Myc is involved in the tumorigenesis of B-lineage acute lymphoblastic leukemia (B-ALL), but the mechanism is not well understood. In the present study, a c-Myc-knockdown model (Raji-KD) was established using Raji cells, and it was indicated that c-Myc regulates the expression of genes associated with cell cycle progression in G2/M-phase, cyclin D kinase (CDK)1 and cyclin B1, by modulating 60 kDa Tat-interactive protein (TIP60)/males absent on the first (MOF)-mediated histone H4 acetylation (AcH4), which was then completely restored by re-introduction of the c-Myc gene into the Raji-KD cells. The expression of CDK1 and cyclin B1 was markedly suppressed in Raji-KD cells, resulting in G2/M arrest. In comparison to Raji cells, the proliferation of Raji-KD cells was significantly reduced, and it was recovered via re-introduction of the c-Myc gene. In the tumorigenesis assays, the loss of c-Myc expression significantly suppressed Raji cell-derived lymphoblastic tumor formation. Although c-Myc also promotes Raji cell apoptosis via the caspase-3-associated pathway, CDK1/cyclin B1-dependent-G2/M cell cycle progression remains the major driving force of c-Myc-controlled tumorigenesis. The present results suggested that c-Myc regulates cyclin B1- and CDK1-dependent G2/M cell cycle progression by TIP60/MOF-mediated AcH4 in Raji cells.