Induction of G1 arrest by down-regulation of cyclin D3 in T cell hybridomas.
The relationship between activation-induced growth inhibition and regulation of the cell cycle progression was investigated in T cell hybridomas by studying the function of the cell cycle-regulating genes such as G1 cyclins and their associated kinases. Activation of T cell hybridomas by anti-T cell receptor antibody induces growth arrest at G1 phase of the cell cycle and subsequently results in activation-driven cell death. Rapid reduction of both messenger RNA and protein level of the cyclin D3 is accompanied by growth arrest upon activation. Although the residual cyclin D3 protein forms a complex with cdk4 protein, cyclin D3-dependent kinase activity is severely impaired. Stable transfectants engineered to express cyclin D3 override the growth arrest upon activation. These results imply that the activation signal through T cell receptor induces the down-regulation of cyclin D3 expression and cyclin D3-dependent kinase activity, leading to growth arrest in G1 phase of the cell cycle in T cells.
Miyatake
S
S
Division of Molecular Genetics, School of Medicine, Chiba University, Japan.
Nakano
H
H
Park
S Y
SY
Yamazaki
T
T
Takase
K
K
Matsushime
H
H
Kato
A
A
Saito
T
T
D000818:Animals; D001483:Base Sequence; D042846:CDC2-CDC28 Kinases; D002453:Cell Cycle; D016923:Cell Death; D056742:Cyclin D2; D056743:Cyclin D3; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism*; D017931:DNA Primers / Q000737:chemistry; D006825:Hybridomas / Q000166:cytology*; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D051379:Mice; D008969:Molecular Sequence Data; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology*
C486196:Ccnd2 protein, mouse; C534697:Ccnd3 protein, mouse; D056742:Cyclin D2; D056743:Cyclin D3; D016213:Cyclins; D017931:DNA Primers; D011518:Proto-Oncogene Proteins; D011948:Receptors, Antigen, T-Cell; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495893:Cdk2 protein, mouse; C495902:Cdk4 protein, mouse; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases