Stat5 tetramer formation is associated with leukemogenesis
Stat5 tetramer formation is associated with leukemogenesis
复制标题
DOI：
10.1016/j.ccr.2004.12.010
复制
发表时间：
2005-01-01
期刊：
影响因子：
50.3
通讯作者：
Beug, H
中科院分区：
文献类型：
--
作者：
Moriggl, R;Sexl, V;Beug, H
Stat 5的激活经常在白血病中发现。为了研究Stat 5激活的机制和作用，我们将组成性激活的Stat 5a突变体cS5（F）导入小鼠骨髓（BM）细胞。用cS5（F）转染细胞进行骨髓移植可导致致死性辐照野生型或未辐照Rag 2（-/-）小鼠发生多系白血病。在DNA结合试验中，白血病细胞显示cS5（F）四聚体水平强烈增强，但cS5（F）二聚体水平不变。此外，Stat 5a突变体经工程改造仅形成二聚体，而不是四聚体，未能诱导白血病。此外，发现Stat 5四聚体在各种人类白血病中与二聚体相比过量积累。这些数据表明Stat 5四聚体与白血病发生相关。
Activation of Stat5 is frequently found in leukemias. To study the mechanism and role of Stat5 activation, we introduced a constitutively activated Stat5a mutant, cS5(F), into murine bone marrow (BM) cells. BM transplantation with cS5(F)-transfected cells caused development of multilineage leukemias in lethally irradiated wild-type or nonirradiated Rag2(-/-) mice. The leukemic cells showed strongly enhanced levels of cS5(F) tetramers but unchanged cS5(F) dimer levels in a DNA binding assay. Moreover, Stat5a mutants engineered to form only dimers, but not tetramers, failed to induce leukemias. In addition, Stat5 tetramers were found to accumulate in excess compared to dimers in various human leukemias. These data suggest that Stat5 tetramers are associated with leukemogenesis.