The retroviral oncoprotein Tax targets the coiled-coil centrosomal protein TAX1BP2 to induce centrosome overduplication.
Emerging evidence suggests that supernumerary centrosomes drive genome instability and oncogenesis. Human T-cell leukaemia virus type I (HTLV-I) is etiologically associated with adult T-cell leukaemia (ATL). ATL cells are aneuploid, but the causes of aneuploidy are incompletely understood. Here, we show that centrosome amplification is frequent in HTLV-I-transformed cells and that this phenotype is caused by the viral Tax oncoprotein. We also show that the fraction of Tax protein that localizes to centrosomes interacts with TAX1BP2, a novel centrosomal protein composed almost entirely of coiled-coil domains. Overexpression of TAX1BP2 inhibited centrosome duplication, whereas depletion of TAX1BP2 by RNAi resulted in centrosome hyperamplification. Our findings suggest that the HTLV-I Tax oncoprotein targets TAX1BP2 causing genomic instability and aneuploidy.
Ching
Yick-Pang
YP
Department of Biochemistry, University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong.
Chan
Shing-Fai
SF
Jeang
Kuan-Teh
KT
Jin
Dong-Yan
DY
D000782:Aneuploidy; D000818:Animals; D016466:CHO Cells; D019556:COS Cells; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D018385:Centrosome / Q000378:metabolism*; D002522:Chlorocebus aethiops; D006224:Cricetinae; D016356:Gene Products, tax / Q000235:genetics / Q000378:metabolism*; D042822:Genomic Instability / Q000502:physiology; D006367:HeLa Cells; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D019169:Jurkat Cells; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000502:physiology; D051381:Rats
D016356:Gene Products, tax; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D034741:RNA, Small Interfering; C494631:VAC14 protein, human