scholarly journals 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

1998 ◽  
Vol 273 (47) ◽  
pp. 31534-31540 ◽  
Author(s):  
Wangsen Cao ◽  
Neeraj Adya ◽  
Martin Britos-Bray ◽  
P. Paul Liu ◽  
Alan D. Friedman
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Smooth Muscle Myosin ◽  
Core Binding Factor ◽  
Interaction Domain ◽  
The Core ◽  
Binding Factor ◽  
Muscle Myosin

scholarly journals The Leukemic Protein Core Binding Factor β (CBFβ)–Smooth-Muscle Myosin Heavy Chain Sequesters CBFα2 into Cytoskeletal Filaments and Aggregates

1998 ◽  
Vol 18 (12) ◽  
pp. 7432-7443 ◽  
Author(s):  
Neeraj Adya ◽  
Terryl Stacy ◽  
Nancy A. Speck ◽  
Pu Paul Liu
Keyword(s):  
Smooth Muscle ◽  
Dna Binding ◽  
Mouse Model ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Chimeric Protein ◽  
Smooth Muscle Myosin ◽  
Core Binding Factor ◽  
Binding Factor ◽  
Muscle Myosin

ABSTRACT The fusion gene CBFB-MYH11 is generated by the chromosome 16 inversion associated with acute myeloid leukemias. This gene encodes a chimeric protein involving the core binding factor β (CBFβ) and the smooth-muscle myosin heavy chain (SMMHC). Mouse model studies suggest that this chimeric protein CBFβ-SMMHC dominantly suppresses the function of CBF, a heterodimeric transcription factor composed of DNA binding subunits (CBFα1 to 3) and a non-DNA binding subunit (CBFβ). This dominant suppression results in the blockage of hematopoiesis in mice and presumably contributes to leukemogenesis. We used transient-transfection assays, in combination with immunofluorescence and green fluorescent protein-tagged proteins, to monitor subcellular localization of CBFβ-SMMHC, CBFβ, and CBFα2 (also known as AML1 or PEBP2αB). When expressed individually, CBFα2 was located in the nuclei of transfected cells, whereas CBFβ was distributed throughout the cell. On the other hand, CBFβ-SMMHC formed filament-like structures that colocalized with actin filaments. Upon cotransfection, CBFα2 was able to drive localization of CBFβ into the nucleus in a dose-dependent manner. In contrast, CBFα2 colocalized with CBFβ-SMMHC along the filaments instead of localizing to the nucleus. Deletion of the CBFα-interacting domain within CBFβ-SMMHC abolished this CBFα2 sequestration, whereas truncation of the C-terminal-end SMMHC domain led to nuclear localization of CBFβ-SMMHC when coexpressed with CBFα2. CBFα2 sequestration by CBFβ-SMMHC was further confirmed in vivo in a knock-in mouse model. These observations suggest that CBFβ-SMMHC plays a dominant negative role by sequestering CBFα2 into cytoskeletal filaments and aggregates, thereby disrupting CBFα2-mediated regulation of gene expression.

Core-binding factor β (CBFβ), but not CBFβ–smooth muscle myosin heavy chain, rescues definitive hematopoiesis in CBFβ-deficient embryonic stem cells

Blood ◽  
2001 ◽  
Vol 97 (8) ◽  
pp. 2248-2256 ◽  
Author(s):  
Janelle D. Miller ◽  
Terryl Stacy ◽  
P. Paul Liu ◽  
Nancy A. Speck
Keyword(s):  
Smooth Muscle ◽  
Fusion Protein ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Es Cells ◽  
Embryonic Stem ◽  
Core Binding Factor ◽  
Binding Factor ◽  
Muscle Myosin ◽  
Definitive Hematopoiesis

Abstract Core-binding factor β (CBFβ) is the non–DNA-binding subunit of the heterodimeric CBFs. Genes encoding CBFβ (CBFB),and one of the DNA-binding CBFα subunits, Runx1 (also known as CBFα2, AML1, and PEBP2αB), are required for normal hematopoiesis and are also frequent targets of chromosomal translocations in acute leukemias in humans. Homozygous disruption of either the Runx1or Cbfb gene in mice results in embryonic lethality at midgestation due to hemorrhaging in the central nervous system, and severely impairs fetal liver hematopoiesis. Results of this study show that Cbfb-deficient mouse embryonic stem (ES) cells can differentiate into primitive erythroid colonies in vitro, but are impaired in their ability to produce definitive erythroid and myeloid colonies, mimicking the in vivo defect. Definitive hematopoiesis is restored by ectopic expression of full-length Cbfbtransgenes, as well as by a transgene encoding only the heterodimerization domain of CBFβ. In contrast, the CBFβ–smooth muscle myosin heavy chain (SMMHC) fusion protein generated by the inv(16) associated with acute myeloid leukemias (M4Eo) cannot rescue definitive hematopoiesis by Cbfb-deficient ES cells. Sequences responsible for the inability of CBFβ-SMMHC to rescue definitive hematopoiesis reside in the SMMHC portion of the fusion protein. Results also show that the CBFβ-SMMHC fusion protein transdominantly inhibits definitive hematopoiesis, but not to the same extent as homozygous loss of Runx1 orCbfb. CBFβ-SMMHC preferentially inhibits the differentiation of myeloid lineage cells, while increasing the number of blastlike cells in culture.

Expression of Desmin and Smooth Muscle Myosin Heavy Chain in Dermatofibromas

2002 ◽  
Vol 126 (10) ◽  
pp. 1179-1183 ◽  
Author(s):  
Andrea K. Bruecks ◽  
Martin J. Trotter
Keyword(s):  
Smooth Muscle ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Smooth Muscle Actin ◽  
Smooth Muscle Myosin ◽  
Immunoperoxidase Staining ◽  
Muscle Actin ◽  
Muscle Myosin ◽  
Hematoxylin Eosin ◽  
Focal Expression

Abstract Background.—The histopathologic features of dermatofibroma vary remarkably, and this diversity may occasionally cause problems in differentiating between benign and malignant mesenchymal lesions, including smooth muscle neoplasms. Immunohistochemical stains are sometimes necessary to clarify the histogenesis of a lesion. Objective.—To evaluate dermatofibromas for expression of desmin and smooth muscle myosin heavy chain (SM-MHC) antigens, which are commonly used as evidence of smooth muscle differentiation. Methods.—We studied 100 consecutive cases of dermatofibroma using hematoxylin-eosin–stained sections and immunoperoxidase staining with antibodies against desmin, SM-MHC, and smooth muscle actin. Results.—We found focal positivity for desmin in 9 cases, and in 2 of these cases, at least 10% of lesional cells showed strong expression. We found focal staining for SM-MHC in 10 cases, and in 2 of these cases, at least 10% of the lesional cells were positive. Regions positive for desmin and/or SM-MHC did not show definite histologic features of myogenous differentiation on hematoxylin-eosin–stained sections. All dermatofibromas expressing desmin and SM-MHC were also strongly positive for smooth muscle actin. Conclusions.—About 10% of dermatofibromas show focal expression of desmin and SM-MHC, and this expression may be present in up to 10% to 15% of lesional cells. Thus, in dermal spindle cell lesions, focal expression of these muscle antigens, like that of smooth muscle actin, is not diagnostic of a smooth muscle tumor.

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