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
Ws. Cao et al., 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, The Journal of biological chemistry, 273(47), 1998, pp. 31534-31540
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.