A centrosomal target of HTLV-I Tax on the road to genome instability

Abstract

Centrosome abnormalities are the cause of genome instability that initiates leukemogenesis. HTLV-I-transformed ATL cells are genomically unstable, but the underlying mechanisms are not clear. We recently demonstrated that centrosome overduplication is frequent in ATL cells and that this phenotype is attributed to the expression of the viral oncoprotein Tax. A fraction of Tax was found in the centrosome, whereby it physically interacted with and inhibited TAX1BP2, a novel coiled-coil protein that is a component of the cellular machinery to block centrosome duplication. Silencing of TAX1BP2 by RNAi caused centrosome hyperamplification. The interaction of Tax with TAX1BP2 interfered with the centrosomal function of the latter, leading to centrosome overduplication as seen in TAX1BP2-depleted cells and ATL cells. Our findings suggest a new mechanism for HTLV-I-induced transformation in which the Tax oncoprotein targets a centrosomal protein causing centrosome-associated genomic instability and aneuploidy.