Phosphorylation by c-Jun NH2-terminal kinase 1 regulates the stability of transcription factor Sp1 during mitosis.
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 NH(2)-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.
Chuang
Jian-Ying
JY
Institute of Basic Medical Sciences, College of Medicine, National Cheng-Kung University, Tainan 701, Taiwan.
Wang
Yi-Ting
YT
Yeh
Shiu-Hwa
SH
Liu
Yi-Wen
YW
Chang
Wen-Chang
WC
Hung
Jan-Jong
JJ
D000818:Animals; D001092:Arachidonate 12-Lipoxygenase / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D008770:Methylnitrosourea; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism*; D008938:Mitosis; D050505:Mutant Proteins / Q000378:metabolism; D009369:Neoplasms / Q000201:enzymology / Q000473:pathology; D010766:Phosphorylation; D010769:Phosphothreonine / Q000378:metabolism; D021381:Protein Transport; D051381:Rats; D017207:Rats, Sprague-Dawley; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D013816:Thermodynamics; D014158:Transcription, Genetic
D050505:Mutant Proteins; D016329:Sp1 Transcription Factor; D010769:Phosphothreonine; D008770:Methylnitrosourea; D001092:Arachidonate 12-Lipoxygenase; D048055:Mitogen-Activated Protein Kinase 8