NF-κB signaling mechanisms in HTLV-1-induced adult T-cell leukemia/lymphoma

Edward William Harhaj, Chou Zen Giam

Research output: Contribution to journalReview article

5 Citations (Scopus)

Abstract

The human T-cell leukemia virus type 1 (HTLV-1) is a complex deltaretrovirus linked to adult T-cell leukemia/lymphoma (ATLL), a fatal CD4 + malignancy in 3–5% of infected individuals. The HTLV-1 Tax regulatory protein plays indispensable roles in regulating viral gene expression and activating cellular signaling pathways that drive the proliferation and clonal expansion of T cells bearing HTLV-1 proviral integrations. Tax is a potent activator of NF-κB, a key signaling pathway that is essential for the survival and proliferation of HTLV-1-infected T cells. However, constitutive NF-κB activation by Tax also triggers a senescence response, suggesting the possibility that only T cells capable of overcoming NF-κB-induced senescence can selectively undergo clonal expansion after HTLV-1 infection. Tax expression is often silenced in the majority of ATLL due to genetic alterations in the tax gene or DNA hypermethylation of the 5′-LTR. Despite the loss of Tax, NF-κB activation remains persistently activated in ATLL due to somatic mutations in genes in the T/B-cell receptor (T/BCR) and NF-κB signaling pathways. In this review, we focus on the key events driving Tax-dependent and -independent mechanisms of NF-κB activation during the multistep process leading to ATLL.

Original languageEnglish (US)
Pages (from-to)3324-3336
Number of pages13
JournalFEBS Journal
Volume285
Issue number18
DOIs
StatePublished - Sep 2018

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Deltaretrovirus
Adult T Cell Leukemia Lymphoma
T-cells
Viruses
Taxation
T-Lymphocytes
pX Genes
tax Gene Products
Viral Genes
Chemical activation
Virus Diseases
T-Cell Antigen Receptor
B-Lymphocytes
Bearings (structural)
Genes
Cell signaling
Gene Expression
Mutation
DNA
Gene expression

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

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title = "NF-κB signaling mechanisms in HTLV-1-induced adult T-cell leukemia/lymphoma",
abstract = "The human T-cell leukemia virus type 1 (HTLV-1) is a complex deltaretrovirus linked to adult T-cell leukemia/lymphoma (ATLL), a fatal CD4 + malignancy in 3–5{\%} of infected individuals. The HTLV-1 Tax regulatory protein plays indispensable roles in regulating viral gene expression and activating cellular signaling pathways that drive the proliferation and clonal expansion of T cells bearing HTLV-1 proviral integrations. Tax is a potent activator of NF-κB, a key signaling pathway that is essential for the survival and proliferation of HTLV-1-infected T cells. However, constitutive NF-κB activation by Tax also triggers a senescence response, suggesting the possibility that only T cells capable of overcoming NF-κB-induced senescence can selectively undergo clonal expansion after HTLV-1 infection. Tax expression is often silenced in the majority of ATLL due to genetic alterations in the tax gene or DNA hypermethylation of the 5′-LTR. Despite the loss of Tax, NF-κB activation remains persistently activated in ATLL due to somatic mutations in genes in the T/B-cell receptor (T/BCR) and NF-κB signaling pathways. In this review, we focus on the key events driving Tax-dependent and -independent mechanisms of NF-κB activation during the multistep process leading to ATLL.",
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NF-κB signaling mechanisms in HTLV-1-induced adult T-cell leukemia/lymphoma. / Harhaj, Edward William; Giam, Chou Zen.

In: FEBS Journal, Vol. 285, No. 18, 09.2018, p. 3324-3336.

Research output: Contribution to journalReview article

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