Ectopic expression of the Aspergillus nidulans mitotic inducer, nimA kinase, in megakaryocytes: Effect on polyploidization

Aspergillus nidulans nimA gene encodes a serine/threonine protein kinase (N IMA) whose activity is essential for mitotic entry and chromatin condensati on. Both the activity and the abundance of NIMA protein increase at the G2/ M transition of the fungal cell cycle. In this study, He report the effects elicited by ectopic expression of nimA on polyploidization in a mouse mega karyocytic line, Y10 which is undergoing an endomitotic cell cycle. A pool of Y10 stable transfectants that hale been induced to express nimA displaye d a decrease in cell number and an elevated DNA content per cell. NIMA also dramatically, enhanced the activity of phorbal 12-myristate 13-acetate ton ard polyploidization. Analysis of individual nial. transfectants revealed that the DNA content per cell rose in tells expressing high levels of nimA and that the level of cyclin B nas reduced as compared to the mock-transfec ted cells. These effects observed in polyploidizing megakaryocytes are in c ontrast to those found in A. nidulans and HeLa cells, in which induced nimA expression caused abnormal chromatin condensation and cell cycle arrest. W e conclude that high-level expression of nimA in cells programmed to underg o endomitosis could potentiate polyploidization. The challenge non resides in the isolation of the authentic megakaryocyte counterpart of the fungal n imA. (C) 1999 International Society for Experimental Published by Elsevier Science Inc.