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J Biol Chem. 1998 Nov 20;273(47):31534-40.

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

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1
Division of Pediatric Oncology, Johns Hopkins Oncology Center, Baltimore, Maryland 21287, USA.

Abstract

We have expressed several variants of core binding factor beta (CBFbeta)-smooth muscle myosin heavy chain (SMMHC) from the metallothionein promoter in Ba/F3 cells. Deletion of amino acids 2-11 from the CBFbeta segment, required for interaction with CBFalpha, prevented CBFbeta-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 CBFbeta-SMMHC. Nuclear expression of CBFbeta(Delta2-11)-SMMHC was decreased relative to CBFbeta-SMMHC. CBFbeta(Delta2-11)-SMMHC linked to a nuclear localization signal still did not slow cell growth. The ability of each CBFbeta-SMMHC variant to inhibit CBF DNA binding and cell proliferation correlated with its ability to inhibit transactivation by an AML1-VP16 fusion protein. Thus, CBFbeta-SMMHC slows cell cycle progression from G1 to S phase by inhibiting CBF DNA binding and transactivation.

PMID:
9813068
[Indexed for MEDLINE]
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