FADD-deficient T cells exhibit a disaccord in regulation of the cell cycle machinery.
FADD is an adapter protein that was originally isolated as a transducer of apoptotic signals for death domain-containing receptors. However, FADD-deficient mice are embryonic lethal and FADD(-/-) T cells developed from FADD(-/-) embryonic stem cells in the RAG-1(-/-) hosts lack the full potential to proliferate when stimulated through their T-cell receptor complex, suggesting that FADD protein might play a dualistic role in mediating not only cell death signaling but other non-apoptotic cellular pathways as well. Here we show that a substantial number of freshly isolated FADD(-/-) peripheral T cells are cycling but are defective in their co-stimulatory response when stimulated. Analysis of several cell cycle proteins shows normal down-regulation of p27 inhibitor but increased levels of p21, decreased levels of cyclin D2, and constitutive activation of several cyclin-dependent kinases in activated T cells. These data suggest that FADD is involved in the regulation of cell cycle machinery in T lymphocytes.
Zhang
J
J
Department of Molecular and Cell Biology, Division of Immunology and Cancer Research Laboratory, University of California at Berkeley, California 94720, USA.
Kabra
N H
NH
Cado
D
D
Kang
C
C
Winoto
A
A
D000818:Animals; D017209:Apoptosis; D029681:Arabidopsis Proteins; D001755:Blastocyst / Q000378:metabolism; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002453:Cell Cycle; D016923:Cell Death; D002455:Cell Division; D056742:Cyclin D2; D016213:Cyclins / Q000096:biosynthesis; D015536:Down-Regulation; D044943:Fatty Acid Desaturases / Q000502:physiology*; D005434:Flow Cytometry; D008213:Lymphocyte Activation; D051379:Mice; D008840:Microfilament Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D009124:Muscle Proteins; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*; D013997:Time Factors
D029681:Arabidopsis Proteins; C486196:Ccnd2 protein, mouse; D056742:Cyclin D2; D016213:Cyclins; D008840:Microfilament Proteins; D009124:Muscle Proteins; D011948:Receptors, Antigen, T-Cell; C058992:Tagln protein, mouse; D044943:Fatty Acid Desaturases; C084083:Fad7 protein, Arabidopsis