Tubedown-1, a novel acetyltransferase associated with blood vessel development

We have used an embryonic endothelial cell line (IEM cells) as an experimen tal system for identifying and characterizing new molecules which are regul ated during blood vessel development. A novel gene isolated from IEM cells, tubedown-1 (tbdn-1), is expressed at high levels in unstimulated IEM cells and is down-regulated during formation of capillary tube structures by the IEM cells induced by basic fibroblast growth factor (bFGF) and leukemia in hibitory factor (LIF) in vitro. Tbdn-1 is also downregulated in M1 myeloid leukemia cells after differentiation in response to LIF in vitro. Tbdn-1 is homologous to the yeast NAT-1 N-terminal acetyltransferases and encodes a novel protein of similar to 69 kDa associated with an acetyltransferase act ivity. Levels and distribution of tbdn-1 expression are regulated in both e ndothelial and hematopoietic cells during development in tissues such as th e yolk sac blood islands, heart, and liver blood vessels. In the adult, tbd n-1 expression is low or undetected in most organs examined with the except ion of the atrial endocardium, the endothelial and myeloid compartments of bone marrow, and the remodeling vascular bed of atretic ovarian follicles. The distribution and regulation of expression of tbdn-1 suggest that this n ovel acetyltransferase may be involved in regulating vascular and hematopoi etic development and physiologic angiogenesis. Dev Dyn 2000;218:300-315. (C ) 2000 Wiley-Liss, Inc.