Functional cooperation of cyclin C and c-Myc in mediating homotypic cell adhesion via very late antigen-4 activation and vascular cell adhesion molecule-1 induction |
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Authors: | ZJ Liu Y Tanaka S Mine A Morinobu H Yagita K Okumura T Taniguchi H Yamamura Y Minami |
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Affiliation: | Department of Biochemistry and of Laboratory Medicine, Kobe University, School of Medicine, Kobe, Japan. |
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Abstract: | Very late antigen-4 (VLA-4)/vascular cell adhesion molecule-1 (VCAM-1) are a pair of adhesion molecules mediating cell-cell interaction. The binding activity of each depends on its surface expression, yet integrin activity can also be modulated through inside-out signaling. However, the specific intracellular molecules involved in modulating integrin VLA-4 activation via inside-out signaling or in regulating VCAM-1 expression are poorly understood. We show here that constitutive coexpression of cyclin C and c-Myc in hematopoietic BAF-B03 cells induces homotypic cell adhesion, which results from enhanced VLA-4 ligand-binding activity and induced expression of VCAM-1. Furthermore, regulation of cell adhesion appears to be a feature unique to cyclin C, but not other G1 cyclins, E and D3, and its regulatory function is independent of CDK8 kinase activity. Our results provide a novel role for cyclin C and c-Myc in the regulation of cell adhesion through distinct mechanisms. |
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