Human T-Cell Leukemia Virus Type 1 (HTLV-1) Tax Requires CADM1/TSLC1 for Inactivation of the NF-κB Inhibitor A20 and Constitutive NF-κB Signaling

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HTLV-1 infection leads to the development of Adult T-cell Leukemia (ATL) or HTLV-1 associated myelopathy/ tropical spastic paraparesis (HAM/TSP). One of the major causes responsible for the development of HTLV-1 associated diseases is chronic inflammation directed by NF-kappaB (NF-κB). NF-κB activation in response to a wide variety of signals is transient and tightly controlled by ubiquitin-editing enzyme A20. One of the mechanisms of persistent NF-κB activation in HTLV-1 infected cells is inactivation of NF-κB negative regulators; however, the precise mechanism is unknown. Here, we focused on host tumor suppressor Cell adhesion molecule 1 (CADM1) that is robustly upregulated in HTLV-1 infected cells. The expression of CADM1 is frequently silenced in several cancers; however, it is critical for HTLV-1 associated ATL tumor cell survival. We characterized the role of CADM1 in persistent NF-κB activation in HTLV-1 infected cells. We found that CADM1 is required for the HTLV-1 oncoprotein, Tax, to form a cellular complex with Ubc13, TAX1BP1, NRP and NEMO in the membrane lipid rafts micorodomain. We further demonstrated that Tax requires CADM1 to inactivate NF-κB negative regulator and maintain persistent NF-κB activation. Our study reveals a novel mechanism of chronic NF-κB activation by CADM1 in HTLV-1 infected cells.

Vyšlo v časopise: Human T-Cell Leukemia Virus Type 1 (HTLV-1) Tax Requires CADM1/TSLC1 for Inactivation of the NF-κB Inhibitor A20 and Constitutive NF-κB Signaling. PLoS Pathog 11(3): e32767. doi:10.1371/journal.ppat.1004721
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004721

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