Human herpesvirus 8 viral FLICE-inhibitory protein retards cell proliferation via downregulation of Id2 and Id3 expression.
Death receptor-mediated apoptosis is potently inhibited by viral FLIP (FLICE/caspase 8 inhibitory protein) through reduced activation of procaspase 8. In this study, we show that the human herpesvirus 8-encoded vFLIP retards cell proliferation. Overexpression of vFLIP caused cell cycle arrest, with an apparent decrease of cells in the S phase. The Id (inhibitor of DNA binding) proteins are considered as dominant negative regulators of differentiation pathways, but positive regulators of cellular proliferation. The mechanisms by which Id proteins promote the cell cycle are diverse, but appear to involve affecting the expression of cell cycle regulators. RT-PCR results demonstrated that the expression of vFLIP decreased the expression levels of Id2 and Id3 as well as cyclin E and cyclin A compared with the vFLIP-null cells. These indicate that vFLIP affects cell proliferation by decreasing the expression levels of cell cycle regulatory proteins.
Wang
Yi-Fen
YF
Department of Medical Technology, Fooyin University, Ta-Liao, Kaohsiung Hsien, Taiwan, ROC. yfwang@mail.fy.edu.tw
Wang
Lin-Yu
LY
Li
Yi-Ling
YL
Shyu
Huey-Wen
HW
Chiou
Yee-Hsuan
YH
Chou
Miao-Chen
MC
Lin
Kuan-Hua
KH
Tai
Ming-Hong
MH
Chen
Chang-Yu
CY
D001483:Base Sequence; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000502:physiology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019925:Cyclin A / Q000378:metabolism; D019927:Cyclin E / Q000378:metabolism; D017931:DNA Primers; D015536:Down-Regulation; D005434:Flow Cytometry; D019288:Herpesvirus 8, Human / Q000378:metabolism*; D006801:Humans; D051797:Inhibitor of Differentiation Protein 2 / Q000378:metabolism*; D051796:Inhibitor of Differentiation Proteins / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D019925:Cyclin A; D019927:Cyclin E; D017931:DNA Primers; C497450:ID2 protein, human; D051797:Inhibitor of Differentiation Protein 2; D051796:Inhibitor of Differentiation Proteins; D009363:Neoplasm Proteins; C075640:ID3 protein, human