Cell cycle-dependent modulation of alpha-interferon-inducible gene expression and activation of signaling components in Daudi cells.
To investigate cell cycle-dependent expression of interferon (IFN)-induced genes and signaling pathways, we examined the modulation of IFN-inducible gene expression and p91 activation, and JAK-1 and Tyk-2 kinases' activation in human Burkitt's lymphoma Daudi cells which were synchronized at different points in the cell cycle progression. We observed that each one of 100-, 67-, and 46-kDa 2'-5'-oligoadenylate synthetase (2-5(A)-synthetase) proteins had a unique expression pattern in different phases of the cell cycle which was different from the expression of 2-5(A)-synthetase proteins in exponentially growing Daudi cells. The cell cycle-dependent changes in the overall levels of expression of 2-5(A)-synthetase proteins correlated well with the induction of expression of 2-5(A)-synthetase mRNA as well as the appearance of IFN stimulatory gene factor-3 and expression and activation of p91 in cells released from the G1/S block in the absence of exogenous IFN-alpha. In addition, cells from the G1/S phase exhibited increased tyrosine phosphorylation of JAK-1 and Tyk-2 kinases and p91 by IFN-alpha as compared with asynchronized cells. Enhanced stimulation of activation of JAK-1, Tyk-2, and p91 by IFN-alpha was progressively reduced from G1/S to G2/M to pass G2/M. These findings demonstrate that the levels of constitutive and inducible expression of IFN-alpha-inducible genes, activation of p91, and tyrosine phosphorylation of JAK-1 and Tyk-2 kinases are differentially influenced by the state of the cell cycle.
Kumar
R
R
Department of Medicine, Pennsylvania State University College of Medicine, Hershey 17033.
Korutla
L
L
Zhang
K
K
D015088:2',5'-Oligoadenylate Synthetase / Q000096:biosynthesis / Q000235:genetics; D001483:Base Sequence; D002051:Burkitt Lymphoma / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004789:Enzyme Activation; D016193:G1 Phase / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D053613:Janus Kinase 1; D008969:Molecular Sequence Data; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D016196:S Phase / Q000502:physiology; D050794:STAT1 Transcription Factor; D015398:Signal Transduction; D053634:TYK2 Kinase; D015534:Trans-Activators; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D016898:Interferon-alpha; D011506:Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D015534:Trans-Activators; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; D053613:Janus Kinase 1; D053634:TYK2 Kinase; C070139:TYK2 protein, human; D015088:2',5'-Oligoadenylate Synthetase