Cytokine-mediated cell survival
Cytokine-mediated cell survival
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DOI：
10.1532/ijh97.04093
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发表时间：
2004-10-01
影响因子：
2.1
通讯作者：
Inaba, T
中科院分区：
文献类型：
--
作者：
Inaba, T
从细胞因子受体发出的信号支持细胞存活的途径长期以来一直是深入研究的焦点。对于Baf-3，一种鼠白细胞介素3依赖性细胞系，涉及的2种不同途径是JAK/STAT/Bcl-x（L）和Ras/PI 3-K。后者通过下调Bim（Bcl-2超家族的仅BH 3细胞死亡激活剂）对于长期细胞存活是必不可少的。因此，Bim很可能是一个关键因素，在造血细胞和神经元细胞中的细胞存活的调节，精氨酸启动。细胞因子（如神经营养因子）至少在3个水平调节Bim表达：（1）在信使RNA（mRNA）水平通过转录调节和可能通过mRNA稳定性，（2）在蛋白质水平通过蛋白酶体依赖性调节蛋白质降解，和（3）通过调节结合动力蛋白运动复合体的潜力影响亚细胞定位。在某些情况下，Bim功能可以以不同的方式调节，使得这3种机制的相对重要性在细胞类型之间可能不同。对于造血，mRNA调控似乎是最重要的。Bim还涉及由Bcr-Abl嵌合酪氨酸激酶和受体酪氨酸激酶的组成型活性突变体引起的白血病发生。(C)2004年日本血液学会。
Pathways through which signals emanating from cytokine receptors support cell survival have long been a focus of intensive research. For Baf-3, a murine interleukin 3-dependent cell line, the 2 distinct pathways involved are JAK/STATs/Bcl-x(L) and Ras/PI3-K. The latter is indispensable for long-term cell survival through down-regulation of Bim, a BH3-only cell death activator of the Bcl-2 superfamily. Thus, Bim is likely to be a key factor for cytokine-initiated regulation of cell survival in both hematopoietic cells and neuronal cells. Cytokines (like neurotrophic factors) regulate Bim expression at at least 3 levels: (1) at the messenger RNA (mRNA) level through transcriptional regulation and possibly through mRNA stability, (2) at the protein level through proteasome-dependent regulation of protein degradation, and (3) by affecting subcellular localization through regulation of the potential to bind to the dynein motor complex. Bim function may be regulated in different ways in certain situations such that the relative importance of these 3 mechanisms may differ among cell types. For hematopoiesis, mRNA regulation seems to be the most important. Bim is also implicated in leukemogenesis caused by the Bcr-Abl chimeric tyrosine kinase and constitutively active mutants of receptor tyrosine kinases. (C) 2004 The Japanese Society of Hematology.