Activation of the CDK7 Gene, Coding for the Catalytic Subunit of the Cyclin-Dependent Kinase (CDK)-Activating Kinase (CAK) and General Transcription Factor II H, by the Trans-Activator Protein Tax of Human T-Cell Leukemia Virus Type-1.

Autor:	Shirasawa M; Department of Biomedical Sciences, School of Biological and Environmental Sciences, Kwansei Gakuin University, 1 Gakuen Uegahara, Sanda 669-1330, Hyogo, Japan., Nakajima R; Department of Biomedical Sciences, School of Biological and Environmental Sciences, Kwansei Gakuin University, 1 Gakuen Uegahara, Sanda 669-1330, Hyogo, Japan., Zhou Y; Department of Biomedical Sciences, School of Biological and Environmental Sciences, Kwansei Gakuin University, 1 Gakuen Uegahara, Sanda 669-1330, Hyogo, Japan., Zhao L; Department of Biomedical Sciences, School of Biological and Environmental Sciences, Kwansei Gakuin University, 1 Gakuen Uegahara, Sanda 669-1330, Hyogo, Japan., Fikriyanti M; Department of Biomedical Sciences, School of Biological and Environmental Sciences, Kwansei Gakuin University, 1 Gakuen Uegahara, Sanda 669-1330, Hyogo, Japan., Iwanaga R; Department of Obstetrics and Gynecology, University of Colorado School of Medicine, Anschutz Medical Campus, 12700 East 19th Avenue, Aurora, CO 80045, USA., Bradford AP; Department of Obstetrics and Gynecology, University of Colorado School of Medicine, Anschutz Medical Campus, 12700 East 19th Avenue, Aurora, CO 80045, USA., Kurayoshi K; Division of Molecular Genetics, Cancer Research Institute, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Ishikawa, Japan., Araki K; Department of Morphological Biology, Ohu University School of Dentistry, 31-1 Misumido Tomitamachi, Koriyama 963-8611, Fukushima, Japan., Ohtani K; Department of Biomedical Sciences, School of Biological and Environmental Sciences, Kwansei Gakuin University, 1 Gakuen Uegahara, Sanda 669-1330, Hyogo, Japan.
Jazyk:	angličtina
Zdroj:	Genes [Genes (Basel)] 2024 Aug 15; Vol. 15 (8). Date of Electronic Publication: 2024 Aug 15.
DOI:	10.3390/genes15081080
Abstrakt:	Human T-cell leukemia virus type-1 (HTLV-1) is the etiological agent of adult T-cell leukemia (ATL). The trans-activator protein Tax of HTLV-1 plays crucial roles in leukemogenesis by promoting proliferation of virus-infected cells through activation of growth-promoting genes. However, critical target genes are yet to be elucidated. We show here that Tax activates the gene coding for cyclin-dependent kinase 7 (CDK7), the essential component of both CDK-activating kinase (CAK) and general transcription factor TFIIH. CAK and TFIIH play essential roles in cell cycle progression and transcription by activating CDKs and facilitating transcriptional initiation, respectively. Tax induced CDK7 gene expression not only in human T-cell lines but also in normal peripheral blood lymphocytes (PHA-PBLs) along with increased protein expression. Tax stimulated phosphorylation of CDK2 and RNA polymerase II at sites reported to be mediated by CDK7. Tax activated the CDK7 promoter through the NF-κB pathway, which mainly mediates cell growth promotion by Tax. Knockdown of CDK7 expression reduced Tax-mediated induction of target gene expression and cell cycle progression. These results suggest that the CDK7 gene is a crucial target of Tax-mediated trans-activation to promote cell proliferation by activating CDKs and transcription.
Databáze:	MEDLINE
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