SCL and LMOI alter thymocyte differentiation:: inhibition of E2A-HEB function and pre-Tα chain expression
SCL and LMOI alter thymocyte differentiation:: inhibition of E2A-HEB function and pre-Tα chain expression
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DOI：
10.1038/77819
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发表时间：
2000-08-01
影响因子：
30.5
通讯作者：
Hoang, T
中科院分区：
文献类型：
--
作者：
Herblot, S;Steff, AM;Hoang, T
干细胞白血病(SCL)转录因子与其核伴侣LMO1或LMO2的协同作用可诱导T细胞急性淋巴细胞性白血病。本研究检测了白血病前期SCL-LMO复合体的细胞和分子靶点。我们发现SCL及其伴侣在最原始的胸腺细胞中共表达。成熟到T细胞前阶段与SCL、LMO1和LMO2下调以及伴随的E2a和Heb表达上调有关。此外，SCL-LMO1的强制表达抑制了T细胞的分化，重演了Heb功能的丧失，导致了从CD4(-)CD8(-)到CD4(+)CD8(+)阶段的过渡检查点的解除调节。最后，我们确定编码PTα的基因是Heb的下游靶标，它被SCL-LMO复合体特异性抑制。
Cooperation between the stem cell leukemia (SCL) transcription factor and its nuclear partners LMO1 or LMO2 induces aggressive T cell acute lymphoblastic leukemia when inappropriately expressed in T cells. This study examined the cellular and molecular targets of the SCL-LMO complex at the preleukemic stage. We show that SCL and its partners are coexpressed in the most primitive thymocytes. Maturation to the pre-T cell stage is associated with a down-regulation of SCL and LMO1 and LMO2, and a concomitant up-regulation of E2A and HEB expression. Moreover, enforced expression of SCL-LMO1 inhibits T cell differentiation and recapitulates a loss of HEB function, causing a deregulation of the transition checkpoint from the CD4(-)CD8(-) to CD4(+)CD8(+) stages. Finally, we identify the gene encoding pT alpha as a downstream target of HEB that is specifically repressed by the SCL-LMO complex.