Human T Cell Leukemia Virus Type I Tax-Induced IκB-ζ Modulates Tax-Dependent and Tax-Independent Gene Expression in T Cells

Kimura, Ryuichiro; Senba, Masachika; Cutler, Samuel J.; Ralph, Stephen John; Xiao, Gutian; Mori, Nozomu

doi:10.1593/neo.131140

Cited by 11 publications

(13 citation statements)

References 70 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A recent study identified the nuclear IκB-ζ to be upregulated in activated B-cell-like subtype of diffuse large B-cell lymphoma (22). We have also reported constitutive expression of IκB-ζ in adult T-cell leukemia cells (23). The hypothesis tested in the present study was that IκB-ζ is induced by LMP-1 and CD30 and that it is also involved in regulation of NF-κB.…”

Section: Introductionsupporting

confidence: 53%

“…The plasmid for truncated TRAF2 protein with retention of only the TRAF domain, ΔTRAF2, has been described previously (32). The human IκB-ζ promoter-luciferase gene constructs have already been described (23,33). The single and combined internal deletion mutants of NF-κB sites were constructed by deletion of the NF-κB sites of the plasmid pGL3-hIκB-ζ(-853) (23).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Induction of IκB-ζ by Epstein-Barr virus latent membrane protein-1 and CD30

Ishikawa

Senba

Mori

2015

International Journal of Oncology

Self Cite

View full text Add to dashboard Cite

Activation of nuclear factor-κB (NF-κB) in Burkitt's lymphoma (BL) and Hodgkin's lymphoma (HL) cells is important in the transformation and development process of these lymphomas. Epstein-Barr virus (EBV) latent membrane protein-1 (LMP-1) and ligand-independent signaling by overexpressed CD30 are known to cause permanent activation of NF-κB in lymphomas. However, hyperactivation of NF-κB triggers cellular senescence and apoptosis. Here, we show that IκB-ζ, an inducible regulator of NF-κB, is constitutively expressed in BL and HL cell lines. In addition, immunohistochemical staining identified nuclear IκB-ζ‑positive BL cells, and Hodgkin and Reed-Sternberg cells in lymph nodes. Expression of LMP-1 and CD30 increased IκB-ζ expression at the transcriptional level. IκB-ζ promoter was regulated by activation of the NF-κB‑inducing kinase (NIK)/IκB kinase/NF-κB pathway via the carboxyl‑terminal tumor necrosis factor (TNF) receptor‑associated factor (TRAF)-interacting regions of LMP-1 and CD30. Interestingly, IκB-ζ inhibited NF-κB activation by LMP-1 and CD30. The results suggest that NF-κB-induced IκB-ζ negatively modulates NF-κB hyperactivation, resulting in a fine balance that ultimately endows a net evolutionary benefit to the survival of BL and HL cells.

show abstract

Section: Introductionsupporting

confidence: 53%

Section: Methodsmentioning

confidence: 99%

Induction of IκB-ζ by Epstein-Barr virus latent membrane protein-1 and CD30

Ishikawa

Senba

Mori

2015

International Journal of Oncology

Self Cite

View full text Add to dashboard Cite

show abstract

“…After 24 h, total RNA was extracted using the RNeasy Plus Mini kit (Qiagen, Hilden, Germany). Microarray analysis using a SurePrint G3 Human GE 8x60 K Microarray kit version 3.0 (Agilent Technologies, Inc., Waldbronn, Germany) was performed as previously described (14).…”

Section: Htlv-1 Infection By Co-cultivationmentioning

confidence: 99%

Mitotic kinase PBK/TOPK as a therapeutic target for adult T‑cell leukemia/lymphoma

2018

Self Cite

View full text Add to dashboard Cite

Adult T‑cell leukemia/lymphoma (ATLL) is a disorder involving human T-cell leukemia virus type 1 (HTLV‑1)-infected T‑cells characterized by increased clonal neoplastic proliferation. PDZ-binding kinase (PBK) [also known as T‑lymphokine-activated killer cell-originated protein kinase (TOPK)] is a serine/threonine kinase expressed in proliferative cells and is phosphorylated during mitosis. In this study, the expression and phosphorylation of PBK/TOPK were examined by western blot analysis and RT‑PCR. We found that PBK/TOPK was upregulated and phosphorylated in HTLV‑1-transformed T‑cell lines and ATLL‑derived T‑cell lines. Notably, CDK1/cyclin B1, which phosphorylates PBK/TOPK, was overexpressed in these cells. HTLV‑1 infection upregulated PBK/TOPK expression in peripheral blood mononuclear cells (PBMCs) in co-culture assays. The potent PBK/TOPK inhibitors, HI‑TOPK‑032, and fucoidan from brown algae, decreased the proliferation and viability of these cell lines in a dose‑dependent manner. By contrast, the effect of HI‑TOPK‑032 on PBMCs was less pronounced. Treatment with HI‑TOPK‑032 resulted in G1 cell cycle arrest, and decreased CDK6 expression and pRb phosphorylation, which are critical determinants of progression through the G1 phase. In addition, HI‑TOPK‑032 induced apoptosis, as evidenced by morphological changes, the cleavage of poly(ADP-ribose) polymerase with the activation of caspase‑3, -8 and -9, and an increase in the sub‑G1 cell population and APO2.7-positive cells. Moreover, HI‑TOPK‑032 inhibited the expression of cellular inhibitor of apoptosis 2 (c-IAP2), X-linked inhibitor of apoptosis protein (XIAP), survivin and myeloid cell leukemia‑1 (Mcl‑1), and induced the expression of Bak and interferon-induced protein with tetratricopeptide repeats (IFIT)1, 2 and 3. It is noteworthy that the use of this inhibitor led to the inhibition of the phosphorylation of IκB kinase (IKK)α, IKKβ, IκBα, phosphatase and tensin homolog (PTEN) and Akt, and to the decreased protein expression of JunB and JunD, suggesting that PBK/TOPK affects the nuclear factor-κB, Akt and activator protein‑1 signaling pathways. In vivo, the administration of HI‑TOPK‑032 suppressed tumor growth in an ATLL xenograft model. Thus, on the whole, this study on the identification and functional analysis of PBK/TOPK suggests that this kinase is a promising molecular target for ATLL treatment.

show abstract

“…We analyzed first the mRNA and protein expression of three Pim kinases in HTLV‐1–infected and HTLV‐1–uninfected T‐cell lines. Constitutive expression of Tax mRNA was noted in HTLV‐1–transformed T‐cell lines, including MT‐2, MT‐4, C5/MJ, SLB‐1, and HUT‐102, but not in ATL–derived T‐cell lines, such as MT‐1, TL‐OmI, and ED‐40515(‐) . Interestingly, Pim‐3 mRNA was detected in all HTLV‐1–infected T‐cell lines, but not in uninfected T‐cell lines except for CCRF‐CEM (Figure A).…”

Section: Resultsmentioning

confidence: 99%