Role of tumor suppressor genes in the development of adult T cell leukemia/lymphoma (ATLL)

Abstract

Adult T cell leukemia/lymphoma (ATLL) is one of the peripheral T cell malignant neoplasms strongly associated with human T cell leukemia virus type-I (HTLV-I). Although the viral transactivating protein Tax

Impact of HTLV-I Tax on cell cycle progression and the cellular DNA damage repair response

“…Alteration of the p53 gene has been observed in 40% of ATL cases (Kinoshita et al, 1992;Sakashita et al, 1992;Yamato et al, 1993), while alterations in p15 INK4B , p16 INK4A , and retinoblastoma (Rb) genes occur in about 30, 35, and 5% of ATL cases, respectively (Hatta et al, 1997a;Suzuki et al, 1999a;Hatta and Koeffler, 2002). Although rare, mutation of p18 INK4C has also been identified in some ATL cells (Hatta et al, 1997b).…”

Molecular mechanisms of cellular transformation by HTLV-1 Tax

“…Rb is epigenetically and genetically inactivated in many cancers (Scrable et al, 1990). In cell cycle studies, many have found that Tax accelerate G1 to S transition (Neuveut et al, 1998;Schmitt et al, 1998;Kehn et al, 2004), providing initial clues that HTLV-1 may inactivate Rb function (Hangaishi et al, 1996;Hatta and Koeffler, 2002). There may be two explanations for how HTLV-1 inactivates Rb.…”

Cellular Transformation by the HTLV-I Tax Protein, a Jack-of-All-Trades

“…An additional disruptive effect of Tax emanates from its impact on the ability of the cell-cycle machinery to regulate DNA replication and cell division (reviewed in Mesnard and Devaux, 1999;Jeang, 2000, 2002;Yoshida, 2001;Hatta and Koeffler, 2002). Progression through various stages of the cell cycle is controlled by different cyclin/cdk (cyclin-dependent kinase) complexes.…”