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 beta (CBF beta)-smooth muscle myosin heavy chain (SMMHC) from the metallothionein promoter in Ba/F3 cells. Deletion of amino acids 2-11 from the CBF beta segment, required for interaction with CBF alpha, prevented CBF beta-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 CBF beta-SMMHC. Nuclear expression of CBF beta(Delta 2-11)-SMMHC was decreased relative to CBF beta-SMMHC. CBF beta(Delta 2-11)-SMMHC linked to a nuclear localization signal still did not slow cell growth. The ability of each CBF beta-SMMHC variant to inhibit CBF DNA binding and cell proliferation correlated with its ability to inhibit transactivation by an AML1-VP16 fusion protein. Thus, CBF beta-SMMHC slows cell cycle progression from G(1) to S phase by inhibiting CBF DNA binding and transactivation.