The core binding factor (CBF) α interaction domain and the smooth muscle myosin heavy chain (SMMHC) segment of CBFβ-SMMHC are both required to slow cell proliferation

We have expressed several variants of core binding factor β (CBFβ)- smooth muscle myosin heavy chain (SMMHC) from the metallothionein promoter in Ba/F3 cells. Deletion of amino acids 2-11 from the CBFβ segment, required for interaction with CBFα, prevented CBFβ-SMMHC from inhibiting CBF DNA binding and cell cycle progression. Deletion of 283 carboxyl-terminal residues from the SMMHC domain, required for multimerization, also inactivated CBFβ-SMMHC. Nuclear expression of CBFβ(Δ2-11)-SMMHC was decreased relative to CBFβ-SMMHC. CBFβ(Δ2-11)-SMMHC linked to a nuclear localization signal still did not slow cell growth. The ability of each CBFβ-SMMHC variant to inhibit CBF DNA binding and cell proliferation correlated with its ability to inhibit transactivation by an AML1-VP16 fusion protein. Thus, CBFβ-SMMHC slows cell cycle progression from G₁ to S phase by inhibiting CBF DNA binding and transactivation.