Repression of AIM-1 kinase mRNA as part of a program of genes regulated by Mpl ligand.

Megakaryocytes give rise to platelets that are essential for thrombosis and hemostasis. During development, megakaryocytes undergo an endomitotic cell cycle by which they skip late anaphase and cytokinesis to yield high ploidy cells. This process is regulated by the c-Mpl receptor ligand. In the current study we used differential display PCR as well as degenerate cloning of kinases to identify part of the program of genes regulated during Mpl ligand-induced differentiation. Several of the induced genes were identified as encoding metabolic proteins as carnitine palmitolytransferase, while other altered genes were identified as encoding kinases. Of these, AIM-1 kinase mRNA was severely downregulated by Mpl ligand at the onset of polyploidy in megakaryocytes. This effect was not related to message stability, but rather to a change in transcriptional rate. These data point to the potential importance of the transcriptional regulation of the AIM-1 gene for promoting megakaryocyte polyploidization. Copyright 2001 Academic Press.