Phosphorylation by c-Jun NH2-terminal kinase 1 regulates the stability of transcription factor Sp1 during mitosis

Jian Ying Chuang, Yi Ting Wang, Shiu Hwa Yeh, Yi Wen Liu, Wen Chang Chang, Jan Jong Hung

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)1139-1151
Number of pages13
JournalMolecular Biology of the Cell
Volume19
Issue number3
DOIs
Publication statusPublished - Mar 2008
Externally publishedYes

Fingerprint

Sp1 Transcription Factor
JNK Mitogen-Activated Protein Kinases
Mitosis
Phosphorylation
Tumor Cell Line
HeLa Cells
Arachidonate 12-Lipoxygenase
Methylnitrosourea
Ubiquitination
Ubiquitin
Glioma
Phosphotransferases
Epithelial Cells
Breast Neoplasms
Gene Expression
Cell Line
Growth

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Phosphorylation by c-Jun NH2-terminal kinase 1 regulates the stability of transcription factor Sp1 during mitosis. / Chuang, Jian Ying; Wang, Yi Ting; Yeh, Shiu Hwa; Liu, Yi Wen; Chang, Wen Chang; Hung, Jan Jong.

In: Molecular Biology of the Cell, Vol. 19, No. 3, 03.2008, p. 1139-1151.

Research output: Contribution to journalArticle

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