Activation of the PI3K-Akt pathway by human T cell leukemia virus type 1 (HTLV-1) oncoprotein Tax increases Bcl3 expression, which is associated with enhanced growth of HTLV-1-infected T cells.
Bcl3 is a member of the IkappaB family that regulates genes involved in cell proliferation and apoptosis. Recent reports indicated that Bcl3 is overexpressed in HTLV-1-infected T cells via Tax-mediated transactivation, and acts as a negative regulator of viral transcription. However, the role of Bcl3 in cellular signal transduction and the growth of HTLV-1-infected T cells have not been reported. In this study, we showed that the knockdown of Bcl3 by short hairpin RNA inhibited the growth of HTLV-1-infected T cells. Although phosphatidylinositol-3 kinase (PI3K) inhibitor reduced Bcl3 expression, inactivation of glycogen synthase kinase 3 (GSK3), an effector kinase of the PI3K/Akt signaling pathway, restored Bcl3 expression in Tax-negative but not in Tax-positive T cells. Our results indicate that the overexpression of Bcl3 in HTLV-1-infected T cells is regulated not only by transcriptional but also by post-transcriptional mechanisms, and is involved in overgrowth of HTLV-1-infected T cells.
Saito
Kousuke
K
Department of Microbiology, Kanazawa Medical University School of Medicine, Ishikawa 920-0293, Japan.
Saito
Mineki
M
Taniura
Naoko
N
Okuwa
Takako
T
Ohara
Yoshiro
Y
D000081242:B-Cell Lymphoma 3 Protein; D002460:Cell Line; D049109:Cell Proliferation; D055785:Gene Knockdown Techniques; D016356:Gene Products, tax / Q000502:physiology*; D015368:Human T-lymphotropic virus 1 / Q000472:pathogenicity*; D006801:Humans; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D013601:T-Lymphocytes / Q000821:virology*; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D037521:Virulence Factors / Q000502:physiology*
D000081242:B-Cell Lymphoma 3 Protein; D016356:Gene Products, tax; D051058:Oncogene Protein v-akt; D019869:Phosphatidylinositol 3-Kinases; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D014157:Transcription Factors; D037521:Virulence Factors; C000631344:BCL3 protein, human; C514970:tax protein, Human T-lymphotrophic virus 1