HTLV-1 tax: Centrosome amplification and cancer

Abstract

During interphase, each cell contains a single centrosome that acts as a microtubule organizing center for cellular functions in interphase and in mitosis. Centrosome amplification during the S phase of the cell cycle is a tightly regulated process to ensure that each daughter cell receives the proper complement of the genome. The controls that ensure that centrosomes are duplicated exactly once in the cell cycle are not well understood. In solid tumors and hematological malignancies, centrosome abnormalities resulting in aneuploidy is observed in the majority of cancers. These phenotypes are also observed in cancers induced by viruses, including adult T cell lymphoma which is caused by the human T cell lymphotrophic virus Type 1 (HTLV-1). Several reports have indicated that the HTLV-1 transactivator, Tax, is directly responsible for the centrosomal abnormalities observed in ATL cells. A recent paper in Nature Cell Biology by Ching et al. has shed some new light into how Tax may be inducing centrosome abnormalities. The authors demonstrated that 30% of ATL cells contained more than two centrosomes and expression of Tax alone induced supernumerary centrosomes. A cellular coiled-coil protein, Tax 1 BP2, was shown to interact with Tax and disruption of this interaction led to failure of Tax to induce centrosome amplification. Additionally, down-regulation of Tax 1 BP2 led to centrosome amplification. These results suggest that Tax 1 BP2 may be an important block to centrosome re-duplication that is observed in normal cells. Presently, a specific cellular protein that prevents centrosome reduplication has not been identified. This paper has provided further insight into how Tax induces centrosome abnormalities that lead to ATL Lastly, additional work on Tax 1 BP2 will also provide insight into how the cell suppresses centrosome re-duplication during the cell cycle and the role that Tax 1 BP2 plays in this important cellular pathway. © 2006 Pumfery et al; licensee BioMed Central Ltd.