Phosphorylation by c-Jun NH2-terminal kinase 1 regulates the stability of transcription factor Sp1 during mitosis
Phosphorylation by c-Jun NH2-terminal kinase 1 regulates the stability of transcription factor Sp1 during mitosis
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DOI：
10.1091/mbc.e07-09-0881
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发表时间：
2008-03-01
影响因子：
3.3
通讯作者：
Hung, Jan-Jong
中科院分区：
文献类型：
--
作者：
Chuang, Jian-Ying;Wang, Yi-Ting;Hung, Jan-Jong
转录因子Sp1在不同细胞中普遍表达，从而调节参与许多细胞过程的基因的表达。这项研究表明，在有丝分裂阶段，在三个上皮肿瘤细胞系和一个胶质瘤细胞系的Sp1磷酸化。通过使用不同的激酶抑制剂，我们发现在HeLa细胞有丝分裂过程中，c-Jun NH 2-末端激酶（JNK）1被激活，然后需要磷酸化Sp1。此外，通过抑制有丝分裂中JNK 1活性来阻断Sp1磷酸化导致Sp1的泛素化和降解。JNK 1在Thr 278/739磷酸化Sp1。在Thr 278/739处突变的Sp1在有丝分裂过程中不稳定，与野生型Sp1相比，在HeLa细胞中具有较低的12（S）-脂氧合酶表达的转录活性，并且表现出降低的细胞生长速率。在N-甲基-N-亚硝基脲诱导的乳腺肿瘤中，JNK 1的激活与Sp1的积累有潜在的相关性。总之，我们的研究结果表明，JNK 1的激活是必要的磷酸化Sp1和屏蔽Sp1从泛素依赖的降解途径在肿瘤细胞系的有丝分裂。
The transcription factor Sp1 is ubiquitously expressed in different cells and thereby regulates the expression of genes involved in many cellular processes. This study reveals that Sp1 was phosphorylated during the mitotic stage in three epithelial tumor cell lines and one glioma cell line. By using different kinase inhibitors, we found that during mitosis in HeLa cells, the c-Jun NH2-terminal kinase (JNK) 1 was activated that was then required for the phosphorylation of Sp1. In addition, blockade of the Sp1 phosphorylation via inhibition JNK1 activity in mitosis resulted in the ubiquitination and degradation of Sp1. JNK1 phosphorylated Sp1 at Thr278/739. The Sp1 mutated at Thr278/739 was unstable during mitosis, possessing less transcriptional activity for the 12(S)-lipoxygenase expression and exhibiting a decreased cell growth rate compared with wild-type Sp1 in HeLa cells. In N-methyl-N-nitrosourea-induced mammary tumors, JNK1 activation provided a potential relevance with the accumulation of Sp1. Together, our results indicate that JNK1 activation is necessary to phosphorylate Sp1 and to shield Sp1 from the ubiquitin-dependent degradation pathway during mitosis in tumor cell lines.