QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 19, Issue 3, 1139-1151, March 2008

This Article Full Text Full Text (PDF) All Versions of this Article: E07-09-0881v1 19/3/1139    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chuang, J.-Y. Articles by Hung, J.-J. Search for Related Content PubMed PubMed Citation Articles by Chuang, J.-Y. Articles by Hung, J.-J.

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^*,,,, and Jan-Jong Hung^,

*Institute of Basic Medical Sciences and Department of Pharmacology, College of Medicine, Institute of Biosignal Transduction, College of Bioscience and Biotechnology, and Center for Gene Regulation and Signal Transduction, National Cheng-Kung University, Tainan 701, Taiwan; and ^||Graduate Institute of Biopharmaceutics, College of Life Sciences, National Chiayi University, Chiayi 600, Taiwan

Submitted September 10, 2007; Revised November 20, 2007; Accepted January 3, 2008
Monitoring Editor: Carl-Henrik Heldin

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.

Address correspondence to: Jan-Jong Hung (janjonghung{at}mac.com) or Wen-Chen Chang (wcchang{at}mail.ncku.edu.tw)

This article has been cited by other articles:

				S. Wei, H.-C. Chuang, W.-C. Tsai, H.-C. Yang, S.-R. Ho, A. J. Paterson, S. K. Kulp, and C.-S. Chen Thiazolidinediones Mimic Glucose Starvation in Facilitating Sp1 Degradation through the Up-Regulation of {beta}-Transducin Repeat-Containing Protein Mol. Pharmacol., July 1, 2009; 76(1): 47 - 57. [Abstract] [Full Text] [PDF]

				P.-H. Huang, D. Wang, H.-C. Chuang, S. Wei, S. K. Kulp, and C.-S. Chen {alpha}-Tocopheryl succinate and derivatives mediate the transcriptional repression of androgen receptor in prostate cancer cells by targeting the PP2A-JNK-Sp1-signaling axis Carcinogenesis, July 1, 2009; 30(7): 1125 - 1131. [Abstract] [Full Text] [PDF]

				H. S. Kim and I. K. Lim Phosphorylated Extracellular Signal-regulated Protein Kinases 1 and 2 Phosphorylate Sp1 on Serine 59 and Regulate Cellular Senescence via Transcription of p21Sdi1/Cip1/Waf1 J. Biol. Chem., June 5, 2009; 284(23): 15475 - 15486. [Abstract] [Full Text] [PDF]

				N. Y. Tan and L. M. Khachigian Sp1 Phosphorylation and Its Regulation of Gene Transcription Mol. Cell. Biol., May 15, 2009; 29(10): 2483 - 2488. [Full Text] [PDF]