Increase in the 64-kDa subunit of the polyadenylation/cleavage stimulatory factor during the Go to S phase transition
Increase in the 64-kDa subunit of the polyadenylation/cleavage stimulatory factor during the Go to S phase transition
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DOI：
10.1073/pnas.95.19.11095
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发表时间：
1998-09-15
影响因子：
11.1
通讯作者：
Milcarek, C
中科院分区：
文献类型：
--
作者：
Martincic, K;Campbell, R;Milcarek, C
在血清诱导的3T6成纤维细胞从G(0)向S的转变和伴随的增殖过程中，多聚腺苷化/切割刺激因子-kDa亚单位(CstF-)的含量增加了5倍。CstF-水平越高，CstF三聚体水平越高。CstF-的升高发生在细胞质中含有Poly(A)的RNA量增加至少5-8倍的时候，原代人脾B细胞停留在G(0)中，在诱导增殖的条件(CD40L暴露)下培养的CstF-显示类似的5倍的增加。因此，CstF-的增加与G(0)到S的相变有关。随着B细胞发育的进展，Ig重链上的RNA处理发生变化，导致从膜上到上游分泌特异性的聚(A)位点的切换。在静息B细胞增殖的同时，用触发这种转换的试剂(CD40L加淋巴因子或金黄色葡萄球菌蛋白A)处理静息B细胞，不会导致CstF-比单独增殖时进一步增加。因此，CstF-的升高不足以诱导分泌。淋巴因子刺激持续生长的B细胞株后，发生向分泌型Ig-MU基因和蛋白的转换，但CstF-水平没有变化，因此，CstF-水平的升高不是介导分化诱导向分泌型Ig-MU重链转换的必要因素。由于CstF-水平的升高对Ig分泌基因的产生既不是必要的，也不是充分的，我们认为其他淋巴因子诱导的因素也起到了作用。
The amount of the 64-kDa subunit of polyadenylation/cleavage stimulatory factor (CstF-64) increases 5-fold during the G(0) to S phase transition and concomitant proliferation induced by serum in 3T6 fibroblasts. Higher levels of CstF-64 result in an increase in CstF trimer. The rise in CstF-64 occurs at a time when the amount of poly(A)-containing RNA rose at least 5-8 fold in the cytoplasm, Primary human splenic B cells, resting in G(0), show a similar 5-fold increase in CstF-64 when cultured under conditions inducing proliferation (CD40 ligand exposure). Therefore, the increase in CstF-64 is associated with the G(0) to S phase transition. As B cell development progresses, RNA processing changes occur at the Ig heavy chain locus resulting in a switch from the membrane- to the upstream secretory-specific poly(A) site. Treating resting B cells with agents triggering this switch in Ig mRNA production along with proliferation (CD40 ligand plus lymphokines or Stapylococcus aureus protein A) induces no further increase in CstF-64 above that seen for proliferation alone. The rise in CstF-64 is therefore insufficient to induce secretion. After stimulation of a continuously growing B cell line with lymphokines, a switch to Ig mu secretory mRNA and protein occurs but without a change in the CstF-64 level, Therefore, an increase in CstF-64 levels is not necessary to mediate the differentiation-induced switch to secreted forms of Ig-mu heavy chain. Because augmentation of CstF-64 levels is neither necessary nor sufficient for Ig secretory mRNA production, we conclude that other lymphokine-induced factors play a role,