THE CORE BINDING-FACTOR (CBF) ALPHA-INTERACTION DOMAIN AND THE SMOOTH-MUSCLE MYOSIN HEAVY-CHAIN (SMMHC) SEGMENT OF CBF-BETA-SMMHC ARE BOTH REQUIRED TO SLOW CELL-PROLIFERATION

We have expressed several variants of core binding factor beta (CBF be ta)-smooth muscle myosin heavy chain (SMMHC) from the metallothionein promoter in Ba/F3 cells. Deletion of amino acids 2-11 from the CBF bet a segment, required for interaction with CBF alpha, prevented CBF beta -SMMHC from inhibiting CBF DNA binding and cell cycle progression. Del etion of 283 carboxyl-terminal residues from the SMMHC domain, require d for multimerization, also inactivated CBF beta-SMMHC. Nuclear expres sion 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 sig nal 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 pro tein. Thus, CBF beta-SMMHC slows cell cycle progression from G(1) to S phase by inhibiting CBF DNA binding and transactivation.