An essential role for Daxx in the inhibition of B lymphopoiesis by type I interferons

An essential role for Daxx in the inhibition of B lymphopoiesis by type I interferons
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DOI:
10.1016/s1074-7613(01)00152-2
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发表时间:
2001-06-01
期刊:
影响因子:
32.4
通讯作者:
Cooper, MD
Cooper, MD
中科院分区:
医学1区
文献类型:
--
作者:
Gongora, R;Stephan, RP;Cooper, MD

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干扰素-α和-β通过一种未知的、STAT 1非依赖性途径抑制白细胞介素-7介导的T和B淋巴祖细胞的生长和存活。β-干扰素处理的祖B细胞的基因表达谱分析显示Daxx表达增强,伴随着Daxx蛋白增加和核体易位。干扰素的作用包括下调细胞周期调控基因和细胞周期阻滞,然后下调Bcl-2和凋亡。Daxx反义寡核苷酸拯救了干扰素处理的pro-B细胞的生长停滞和凋亡与核Daxx的减少平行。这些发现暗示了Daxx在干扰素诱导的淋巴祖细胞凋亡中的基因抑制功能。
Interferon-alpha and -beta inhibit the interleukin-7-mediated growth and survival of T and B lymphoid progenitors via an unknown, STAT1-independent pathway. Gene expression profile analysis of interferon-beta -treated progenitor B cells revealed enhanced Daxx expression, with concomitant Daxx protein increase and nuclear body translocation. The interferon effects included downregulation of cell cycle regulating genes and cell cycle arrest, followed by Bcl-2 downregulation and apoptosis. Daxx antisense oligonucleotides rescued the interferon-treated pro-B cells from growth arrest and apoptosis in parallel with the reduction of nuclear Daxx. These findings implicate the gene repressor function of Daxx in interferon-induced apoptosis of lymphoid progenitors.