Sumoylation of Specificity Protein 1 Augments Its Degradation by Changing the Localization and Increasing the Specificity Protein 1 Proteolytic Process

Yi Ting Wang, Jian Ying Chuang, Meng Ru Shen, Wen Bin Yang, Wen Chang Chang, Jan Jong Hung

Research output: Contribution to journalArticle

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Abstract

Although specificity protein 1 (Sp1) accumulation has been found in various tumor strains, its mechanism is still not very clear. Herein, we found that modification of Sp1 by SUMO-1 facilitates Sp1 degradation. Our findings revealed that, although the amounts of Sp1 and Sp1 mutant (K16R) [Sp1(K16R)] mRNA in cells were equal, the protein level of Sp1(K16R) was higher than that of wild-type Sp1. We also proved that this sumoylation site was not the residue at which ubiquitination occurred. In vitro and in vivo pull-down assays revealed that more sumoylated Sp1 was localized in the cytoplasm, and the interaction between SUMO-1-Sp1 and the proteasome subunit rpt6 in HeLa cells was enhanced. In addition, although Sp1 accumulated in the tumorous cervical tissue, it was not prone to sumoylation. Finally, by overexpression of HA (hemagglutinin)-SUMO-1-Sp1-myc, HA-Sp1-myc, and HA-Sp1(K16R), we found that modification of Sp1 by SUMO-1 was important for Sp1 proteolysis. In conclusion, modification of Sp1 by SUMO-1 altered its localization and then increased its interaction with rpt6. This interaction increased the efficiency of Sp1 proteolytic processing and ubiquitination and then resulted in Sp1 degradation. Therefore, sumoylation of Sp1 is attenuated during tumorigenesis in order to increase Sp1 stability.

Original languageEnglish
Pages (from-to)869-885
Number of pages17
JournalJournal of Molecular Biology
Volume380
Issue number5
DOIs
Publication statusPublished - Jul 25 2008
Externally publishedYes

Fingerprint

Sumoylation
SUMO-1 Protein
Proteins
Proteolysis
Ubiquitination
Protein Stability
Proteasome Endopeptidase Complex
Mutant Proteins
HeLa Cells

Keywords

  • cervical cancer
  • rpt6
  • Sp1
  • sumoylation
  • ubiquitination

ASJC Scopus subject areas

  • Virology

Cite this

Sumoylation of Specificity Protein 1 Augments Its Degradation by Changing the Localization and Increasing the Specificity Protein 1 Proteolytic Process. / Wang, Yi Ting; Chuang, Jian Ying; Shen, Meng Ru; Yang, Wen Bin; Chang, Wen Chang; Hung, Jan Jong.

In: Journal of Molecular Biology, Vol. 380, No. 5, 25.07.2008, p. 869-885.

Research output: Contribution to journalArticle

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AU - Yang, Wen Bin

AU - Chang, Wen Chang

AU - Hung, Jan Jong

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AB - Although specificity protein 1 (Sp1) accumulation has been found in various tumor strains, its mechanism is still not very clear. Herein, we found that modification of Sp1 by SUMO-1 facilitates Sp1 degradation. Our findings revealed that, although the amounts of Sp1 and Sp1 mutant (K16R) [Sp1(K16R)] mRNA in cells were equal, the protein level of Sp1(K16R) was higher than that of wild-type Sp1. We also proved that this sumoylation site was not the residue at which ubiquitination occurred. In vitro and in vivo pull-down assays revealed that more sumoylated Sp1 was localized in the cytoplasm, and the interaction between SUMO-1-Sp1 and the proteasome subunit rpt6 in HeLa cells was enhanced. In addition, although Sp1 accumulated in the tumorous cervical tissue, it was not prone to sumoylation. Finally, by overexpression of HA (hemagglutinin)-SUMO-1-Sp1-myc, HA-Sp1-myc, and HA-Sp1(K16R), we found that modification of Sp1 by SUMO-1 was important for Sp1 proteolysis. In conclusion, modification of Sp1 by SUMO-1 altered its localization and then increased its interaction with rpt6. This interaction increased the efficiency of Sp1 proteolytic processing and ubiquitination and then resulted in Sp1 degradation. Therefore, sumoylation of Sp1 is attenuated during tumorigenesis in order to increase Sp1 stability.

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