Murine FGF-Inducible Kinase is Rapidly Degraded via the Nuclear Ubiquitin-Proteosome System When Overexpressed in NIH 3T3 Cells
Murine FGF-Inducible Kinase is Rapidly Degraded via the Nuclear Ubiquitin-Proteosome System When Overexpressed in NIH 3T3 Cells
复制标题
当小鼠 FGF 诱导激酶在 NIH 3T3 细胞中过表达时，会通过核泛素-蛋白酶体系统快速降解
作者：
G. F. Alberts;J. Winkles
FGF诱导型激酶（Fnk）是结构相关的丝氨酸/苏氨酸蛋白激酶的polo样激酶家族的成员。这些激酶似乎在正常细胞周期进程和DNA损伤反应中起关键作用。在Fnk的情况下，一些报告表明，这种蛋白质通常在细胞中作为应激激活的检查点激酶发挥作用。然而，当Fnk在细胞中异位过表达时，它可能会被组成性激活，这会促进细胞周期停滞和凋亡。在本文中，我们报告了小鼠Fnk在转染的NIH 3 T3成纤维细胞中短暂过表达时半衰期较短。相反，当激酶缺陷型Fnk突变蛋白Fnk-K92 M在转染细胞中过表达时，其显著更稳定。我们还发现，Fnk野生型（WT）和Fnk-K92 M存在于转染细胞的细胞核和细胞质中，并且Fnk核输出需要CRM 1功能。这两种蛋白质都通过细胞核泛素-蛋白体系统在细胞中降解;然而，Fnk-K92 M不像Fnk-WT那样有效地进入细胞核区室，因此它明显更稳定。这些结果表明，Fnk在转染细胞中的表达水平可以通过核质运输，泛素化和蛋白酶体依赖性降解来调节。此外，我们的研究表明，下调内源性Fnk活性在应激细胞中可能会发生，至少部分，通过Fnk核转位和蛋白体降解。
FGF-inducible kinase (Fnk) is a member of the polo-like kinase family of structurally-related serine/threonine protein kinases. These kinases appear to play critical roles in normal cell cycle progression and in the DNA damage response. In the case of Fnk, several reports indicate that this protein normally functions in cells as a stress-activated checkpoint kinase. However, when Fnk is ectopically overexpressed in cells, it likely becomes constitutively activated, and this promotes cell cycle arrest and apoptosis. In the present paper, we report that murine Fnk has a short half-life when transiently overexpressed in transfected NIH 3T3 fibroblasts. In contrast, when a kinase-deficient Fnk mutant protein, Fnk-K92M, is overexpressed in transfected cells, it is significantly more stable. We also found that Fnk-wild-type (WT) and Fnk-K92M are present in both the nucleus and cytoplasm of transfected cells and that Fnk nuclear export requires CRM1 function. Both of these proteins are degraded in cells via the nuclear ubiquitin-proteosome system; however, Fnk-K92M does not enter the nuclear compartment as efficiently as Fnk-WT and consequently it is significantly more stable. These results demonstrate that Fnk expression levels in transfected cells can be regulated by nuclear-cytoplasmic trafficking, ubiquitination, and proteosome-dependent degradation. Furthermore, our studies indicate that the down-regulation of endogenous Fnk activity in stressed cells may occur, at least in part, by Fnk nuclear translocation and proteosomal degradation.
影响因子：
3.3
作者：
Maiyar, AC;Leong, MLL;Firestone, GL
通讯作者：
Firestone, GL
影响因子：
3.5
作者：
HO, SN;HUNT, HD;PEASE, LR
通讯作者：
PEASE, LR
哺乳动物 Polo 样激酶 Plk3 过度表达导致不完全胞质分裂和细胞凋亡诱导。
DOI：
--
发表时间：
2000
期刊：
Cancer research.
影响因子：
--
作者：
Conn,CW;Hennigan,RF;Dai,W;Sanchez,Y;Stambrook,PJ
通讯作者：
Stambrook,PJ