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.
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.
Cao
W
W
Division of Pediatric Oncology, Johns Hopkins Oncology Center, Baltimore, Maryland 21287, USA.
Adya
N
N
Britos-Bray
M
M
Liu
P P
PP
Friedman
A D
AD
D001854:Bone Marrow Cells; D002451:Cell Compartmentation; D002455:Cell Division; D050660:Core Binding Factors; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D006131:Growth Inhibitors / Q000378:metabolism*; D006410:Hematopoiesis / Q000235:genetics*; D007938:Leukemia / Q000235:genetics; D008221:Lymphoid Tissue / Q000166:cytology; D008668:Metallothionein / Q000235:genetics; D009130:Muscle, Smooth; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism*; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017384:Sequence Deletion; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D014178:Translocation, Genetic
D050660:Core Binding Factors; D004268:DNA-Binding Proteins; D006131:Growth Inhibitors; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D010446:Peptide Fragments; D014157:Transcription Factors; D008668:Metallothionein; D018995:Myosin Heavy Chains