Activation of PKC-δ in HTLV-1-infected T cells

摘要: Protein kinase C (PKC)-δ is a member of the PKC family. It has been implicated in tumor suppression as well survival various cancers. The aggressive malignancy T lymphocytes known adult T-cell leukemia (ATL) associated with human virus type 1 (HTLV-1) infection. In this study, we show that HTLV-1-infected cells are characterized by phosphorylation and nuclear translocation PKC-δ. Expression HTLV-1 regulatory protein Tax increased PKC-δ phosphorylation. Blockade rottlerin suppressed inhibited cell viability lines primary ATL cells. Rottlerin induced cycle arrest at G1 phase caspase-mediated apoptosis downregulated expression proteins involved G1/S transition, cyclin D2, CDK4 6, c-Myc, resulting dephosphorylation retinoblastoma (pRb). Furthermore, reduced important anti-apoptotic (e.g., survivin, XIAP, Bcl-xL c-FLIP) Bcl-2 phosphorylation, activated pro-apoptotic Bax. Our results showed permanent activation factor-κB (NF-κB) allows infected to escape mediates Tax-induced NF-κB. Based on these findings, new therapies designed target could be potentially useful treatment ATL.