Expression and stabilization of the MCT-1 protein by DNA damaging agents

The contribution of oncogene amplification and/or overexpression to T-cell lymphoid neoplasms has only of late been established with the implication of the TCL1 and MTCP1 genes in T-cell malignancies. Our laboratory has recently discovered a novel oncogene, MCT-1, amplified in a T-cell lymphoma and mapped to chromosome Xq22-24. MCT-1 has been shown to decrease cell-doubling time, dramatically shortening the duration of G(1) transit time and/or G1-S transition, and transforms NIH3T3 fibroblasts. Constitutive expression of MCT-1 results in a strong proliferative signal and is associated with deregulation of protein kinase-mediated G1/S phase checkpoints. In this study we analysed the level and subcellular localization of this novel cell cycle regulatory molecule as a function of cell cycle phase. In human lymphoid tumors expression of MCT-1 is constant throughout the cell cycle and remains cytoplasmic. Cells overexpressing MCT-1 have increased expression of cyclin D1 with dysregulation of the G(1)-S checkpoint. Both cyclin D1 and MCT-1 are involved in regulating passage of cells through the G1 phase of the cell cycle. Since prior work has shown that gamma irradiation induces cyclin D1 expression we investigated the induction of MCT-1 to DNA damaging agents. We demonstrate that increases in MCT-1 protein in irradiated human lymphoid cells do not occur at the mRNA level and do not require new protein synthesis.