Hematologic effects of inactivating the Ras processing enzyme Rce1

被引:16
作者
Aiyagari, AL
Taylor, BR
Aurora, V
Young, SG
Shannon, KM
机构
[1] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA
[2] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA
[3] Univ Calif San Francisco, Gladstone Inst Cardiovasc Dis, San Francisco, CA 94143 USA
[4] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA
关键词
D O I
10.1182/blood-2002-07-2250
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Posttranslational processing of Ras proteins has attracted considerable interest as a potential target for anticancer drug discovery. Rce1 encodes an endoprotease that facilitates membrane targeting of Ras and other prenylated proteins by releasing the carboxyl-terminal 3 amino acids (ie, the -AAX of the CAAX motif). Homozygous Rce1 mutant embryos (Rce1(-/-)) die late in gestation. To characterize the role of Rce1 in hematopoiesis, we performed adoptive transfers and investigated cells from the recipients. Rce1(-/-) fetal liver cells rescued lethally irradiated recipients and manifested normal long-term repopulating potential in competitive repopulation assays. The recipients of Rce1(-/-) cells developed modest elevations in mature myeloid cells (neutrophils + monocytes), but remained well. Bone marrow cells from mice that received transplants of Rce1(-/-) activated extracellular signal-related kinase (ERK) normally in response to granulocyte-macrophage colony-stimulating factor. These data suggest that pharmacologic inhibitors of Rce1 will have minimal effects on normal hematopoietic cells.
引用
收藏
页码:2250 / 2252
页数:3
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