Heym S, Mohr C, Engelbrecht HC, Fleckenstein B, Thoma-Kreß A (2022)
Publication Type: Journal article
Publication year: 2022
Book Volume: 14
Journal Issue: 3
Simple Summary:& nbsp;The actin-bundling protein Fascin is upregulated in many types of cancers, including adult T-cell leukemia/lymphoma, a tumor induced by the oncogenic retrovirus human T-cell leukemia virus type 1 (HTLV-1). Transcriptional regulation of Fascin is heterogeneous between different cell types and tissues, and Fascin is usually expressed at low levels in T-cells. We have previously shown that a single viral oncoprotein, Tax-1 of HTLV-1, is a potent inducer of Fascin in T-cells depending on classical NF-kappa B signaling. In this study, we discovered that transcriptional activation of Fascin by viral oncoproteins depends on activity of both the classical and the alternative NF-kappa B signaling cascade. Comparisons between Tax-1 and Tax-2 from the closely related but non-oncogenic HTLV-2 revealed that alternative NF-kappa B signaling discriminates transcriptional induction of Fascin by the Tax proteins encoded by HTLVs. Together, Tax-1 and Tax-2 proteins are useful tools to study oncogenic signaling in T-cells.& nbsp;Transcriptional regulation of the actin-bundling protein and tumor marker Fascin is highly diverse depending on cell and tumor type. Previously, we discovered that the viral oncoprotein Tax-1 of human T-cell leukemia virus type 1 (HTLV-1) considerably enhances Fascin expression in T-cells, depending on classical NF-kappa B signaling. In this study, we asked if the non-oncogenic Tax-2 of the related HTLV-2 is still able to induce Fascin by using luciferase assays, immunoblot, and qPCR. We found that Tax-2 only slightly induces Fascin expression compared to Tax-1; however, both Tax-1 and Tax-2 comparably activated a 1.6 kb fragment in the human Fascin promoter including Tax-responsive elements. Furthermore, we identified a link between Tax-induced activity of the alternative NF-kappa B pathway and Fascin induction. While treatment with the second mitochondria-derived activator of caspases (SMAC)-mimetic AZD5582, a compound known to robustly activate alternative NF-kappa B signaling, did not induce Fascin, combination of AZD5582 with activation of classical NF-kappa B signaling by Tax-2 significantly induced Fascin expression. In conclusion, our data demonstrate that both classical and alternative NF-kappa B activity are necessary for strong Fascin induction by the viral Tax oncoproteins, thus, shedding new light on the regulation of Fascin in T-cells and during viral transformation.
APA:
Heym, S., Mohr, C., Engelbrecht, H.C., Fleckenstein, B., & Thoma-Kreß, A. (2022). Alternative NF-kappa B Signaling Discriminates Induction of the Tumor Marker Fascin by the Viral Oncoproteins Tax-1 and Tax-2 of Human T-Cell Leukemia Viruses. Cancers, 14(3). https://dx.doi.org/10.3390/cancers14030537
MLA:
Heym, Stefanie, et al. "Alternative NF-kappa B Signaling Discriminates Induction of the Tumor Marker Fascin by the Viral Oncoproteins Tax-1 and Tax-2 of Human T-Cell Leukemia Viruses." Cancers 14.3 (2022).
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