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.
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.
Liu
Z J
ZJ
Department of Biochemistry and of Laboratory Medicine, Kobe University, School of Medicine, Kobe, Japan.
Tanaka
Y
Y
Mine
S
S
Morinobu
A
A
Yagita
H
H
Okumura
K
K
Taniguchi
T
T
Yamamura
H
H
Minami
Y
Y
D000818:Animals; D019138:Antibodies, Blocking / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules; D002453:Cell Cycle / Q000502:physiology; D002455:Cell Division; D002460:Cell Line; D056745:Cyclin C; D056850:Cyclin-Dependent Kinase 8; D018844:Cyclin-Dependent Kinases; D016213:Cyclins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D004789:Enzyme Activation; D006412:Hematopoietic Stem Cells / Q000201:enzymology; D006801:Humans; D039441:Integrin alpha4; D039041:Integrin alpha4beta1; D019012:Integrin beta1; D016023:Integrins / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism* / Q000502:physiology; D016029:Receptors, Very Late Antigen; D014162:Transfection; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
D019138:Antibodies, Blocking; D015703:Antigens, CD; C503674:CCNC protein, human; C503675:Ccnc protein, mouse; D015815:Cell Adhesion Molecules; D056745:Cyclin C; D016213:Cyclins; D039041:Integrin alpha4beta1; D019012:Integrin beta1; D016023:Integrins; D016271:Proto-Oncogene Proteins c-myc; D016201:Receptors, Lymphocyte Homing; D016029:Receptors, Very Late Antigen; D019010:Vascular Cell Adhesion Molecule-1; D039441:Integrin alpha4; D017346:Protein Serine-Threonine Kinases; C095686:CDK8 protein, human; D056850:Cyclin-Dependent Kinase 8; D018844:Cyclin-Dependent Kinases