Genome-wide expression changes induced by HTLV-1 Tax: evidence for MLK-3 mixed lineage kinase involvement in Tax-mediated NF-kappaB activation.
The Tax protein of human T-lymphotropic virus type 1 (HTLV-1), an oncoprotein that transactivates viral and cellular genes, plays a key role in HTLV-1 replication and pathogenesis. We used cDNA microarrays to examine Tax-mediated transcriptional changes in the human Jurkat T-cell lines JPX-9 and JPX-M which express Tax and Tax-mutant protein, respectively, under the control of an inducible promoter. Approximately 300 of the over 2000 genes examined were differentially expressed in the presence of Tax. These genes were grouped according to their function and are discussed in the context of existing findings in the literature. There was strong agreement between our results and genes previously reported as being Tax-responsive. Genes that were differentially expressed in the presence of Tax included those related to apoptosis, the cell cycle and DNA repair, signaling factors, immune modulators, cytokines and growth factors, and adhesion molecules. Functionally, we provide evidence that one of these genes, the mixed-lineage kinase MLK-3, is involved in Tax-mediated NF-kappa-B signaling. Our current results provide additional insights into Tax-mediated signaling.
Ng
P W
PW
HIV and AIDS Malignancy Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Iha
H
H
Iwanaga
Y
Y
Bittner
M
M
Chen
Y
Y
Jiang
Y
Y
Gooden
G
G
Trent
J M
JM
Meltzer
P
P
Jeang
K T
KT
Zeichner
S L
SL
D017209:Apoptosis / Q000235:genetics; D015153:Blotting, Western; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D016356:Gene Products, tax / Q000502:physiology*; D016355:Genes, pX; D006133:Growth Substances / Q000096:biosynthesis / Q000235:genetics; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D020930:MAP Kinase Kinase Kinases / Q000502:physiology*; D016328:NF-kappa B / Q000502:physiology*; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014157:Transcription Factors / Q000502:physiology; D015533:Transcriptional Activation; D000097767:Mitogen-Activated Protein Kinase Kinase Kinase 11
D015815:Cell Adhesion Molecules; D016207:Cytokines; D016356:Gene Products, tax; D006133:Growth Substances; D020930:MAP Kinase Kinase Kinases; D016328:NF-kappa B; D009363:Neoplasm Proteins; D014157:Transcription Factors; D000097767:Mitogen-Activated Protein Kinase Kinase Kinase 11