Zhang Y, Sun S, Chen W C, Kaluzhny Y, Chinnappan D, Yu G, Ravid K
Department of Biochemistry and Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
Biochem Biophys Res Commun. 2001 Apr 6;282(3):844-9. doi: 10.1006/bbrc.2001.4635.
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.
巨核细胞产生对血栓形成和止血至关重要的血小板。在发育过程中，巨核细胞经历一种核内有丝分裂细胞周期，通过该周期它们跳过后期和胞质分裂以产生高倍体细胞。这个过程由c-Mpl受体配体调节。在当前研究中，我们使用差异显示PCR以及激酶的简并克隆来鉴定在Mpl配体诱导的分化过程中受调控的部分基因程序。几个诱导基因被鉴定为编码代谢蛋白，如肉碱棕榈酰转移酶，而其他改变的基因被鉴定为编码激酶。其中，AIM-1激酶mRNA在巨核细胞多倍体形成开始时被Mpl配体严重下调。这种效应与信息稳定性无关，而是与转录速率的变化有关。这些数据表明AIM-1基因的转录调控对促进巨核细胞多倍体化具有潜在重要性。
