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1.  Expression of p89c-Mybex9b, an alternatively spliced form of c-Myb, is required for proliferation and survival of p210BCR/ABL-expressing cells 
Blood Cancer Journal  2012;2(5):e71-.
The c-Myb gene encodes the p75c-Myb isoform and less-abundant proteins generated by alternatively spliced transcripts. Among these, the best known is pc-Mybex9b, which contains 121 additional amino acids between exon 9 and 10, in a domain involved in protein–protein interactions and negative regulation. In hematopoietic cells, expression of pc-Mybex9b accounts for 10–15% of total c-Myb; these levels may be biologically relevant because modest changes in c-Myb expression affects proliferation and survival of leukemic cells and lineage choice and frequency of normal hematopoietic progenitors. In this study, we assessed biochemical activities of pc-Mybex9b and the consequences of perturbing its expression in K562 and primary chronic myeloid leukemia (CML) progenitor cells. Compared with p75c-Myb, pc-Mybex9b is more stable and more effective in transactivating Myb-regulated promoters. Ectopic expression of pc-Mybex9b enhanced proliferation and colony formation and reduced imatinib (IM) sensitivity of K562 cells; conversely, specific downregulation of pc-Mybex9b reduced proliferation and colony formation, enhanced IM sensitivity of K562 cells and markedly suppressed colony formation of CML CD34+ cells, without affecting the levels of p75c-Myb. Together, these studies indicate that expression of the low-abundance pc-Mybex9b isoform has an important role for the overall biological effects of c-Myb in BCR/ABL-transformed cells.
doi:10.1038/bcj.2012.16
PMCID: PMC3366069  PMID: 22829973
transcription factor; oncogene; chronic myeloid leukemia
2.  Influence of hemodynamic forces on vascular endothelial function. In vitro studies of shear stress and pinocytosis in bovine aortic cells. 
Journal of Clinical Investigation  1984;73(4):1121-1129.
The relationships between fluid shear stress, a physiologically relevant mechanical force in the circulatory system, and pinocytosis (fluid-phase endocytosis) were investigated in cultured bovine aortic endothelial cells using a specially designed apparatus. Continuous exposure to steady shear stresses (1-15 dyn/cm2) in laminar flow stimulated time- and amplitude-dependent increases in pinocytotic rate which returned to control levels after several hours. After 48 h continuous exposure to steady shear stress, removal to static conditions also resulted in a transient increase in pinocytotic rate, suggesting that temporal fluctuations in shear stress may influence endothelial cell function. Endothelial pinocytotic rates remained constant during exposure to rapidly oscillating shear stress at near physiological frequency (1 Hz) in laminar flow. In contrast, however, a sustained elevation of pinocytotic rate occurred when cells were subjected to fluctuations in shear stress amplitude (3-13 dyn/cm2) of longer cycle time (15 min), suggesting that changes in blood flow of slower periodicity may influence pinocytotic vesicle formation. As determined by [3H]thymidine autoradiography, neither steady nor oscillating shear stress stimulated the proliferation of confluent endothelial cells. These observations indicate that: (a) alterations in fluid shear stress can significantly influence the rate of formation of pinocytotic vesicles in vascular endothelial cells, (b) this process is force- and time-dependent and shows accommodation, (c) certain patterns of fluctuation in shear stress result in sustained elevation of pinocytotic rate, and (d) shear stresses can modulate endothelial pinocytosis independent of growth stimulation. These findings are relevant to (i) transendothelial transport and the metabolism of macromolecules in normal endothelium and (ii) the role of hemodynamic factors in the localization of atherosclerotic lesions in vivo.
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PMCID: PMC425126  PMID: 6707208

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