TCL1 promotes blastomere proliferation through nuclear transfer, but not direct phosphorylation, of AKT/PKB in early mouse embryos

The T-cell leukemia/lymphoma 1 (TCL1) gene is expressed during T-cell and B-cell development and involved in the pathogenesis of T-cell and B-cell leukemias/ lymphomas. It also plays a key regulatory role in the maintenance of the proliferation versus differentiation balance of embryonic stem (ES) cells. We previously characterized the expression of TCL1 during preimplantation embryo development, namely in the cells from which ES cells are derived, and found that it shuttles between blastomere cortical regions and the nucleus by a cell cycle-dependent fashion and to be required for early blastomere proliferation, but not the acquisition of first embryonal differentiation traits. TCL1 promotes cell proliferation by heterodimerization with AKT/PKB, a serine/threonine kinase having a central role in the signaling pathways controlling cell proliferation and survival. We have now analyzed TCL1/AKT interaction in the preimplantation mouse embryo and found that TCL1 is not relevant to AKT phosphorylation in one-cell and two-cell embryos. Therefore, early mouse embryos display a physiological dissociation between the TCL1 functions of AKT phosphorylation and phosphorylated AKT transfer to nucleus, pinpointing the latter function as the essential one for the AKT-mediated promotion of cell proliferation. We also provide evidence that TCL1 enters one-cell embryo pronuclei, while phosphorylated AKT does not, suggesting that TCL1 also plays an AKT independent role(s) at the beginning of embryo development.