MAPK and JNK transduction pathways can phosphorylate Sp1 to activate the uPA minimal promoter element and endogenous gene transcription

Elisa Benasciutti, Gilles Pagès, Olga Kenzior, William Folk, Francesco Blasi, Massimo P. Crippa

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

Two upstream regions of the human urokinase (uPA) gene regulate its transcription: the minimal promoter (MP) and the enhancer element. The activity of the minimal promoter is essential for basal uPA transcription in prostate adenocarcinoma PC3 cells. Binding of a phosphorylated Sp1 transcription factor is, in turn, essential for the activity of the MP. Here we report that the Jun kinase (JNK) pathway is required for the basal activity of the MP and for the expression of the endogenous uPA gene in PC3 cells and for activated transcription in LNCaP cells. On the other hand, the p42/p44 mitogen-activated protein kinase (MAPK) pathway activates uPA gene expression through Sp1 phosphorylation in HeLa, LNCaP, and CCL39-derivative cells that do not typically express uPA in basal conditions. In HeLa cells the dominant-negative form of JNK interferes with the p42/p44 MAPK activation of the uPA-MP. The results suggest that the stress-activated protein kinase (SAPK)/JNK pathway plays an important role in the phosphorylation of Sp1, which, in turn, leads to basal or activated transcription from the uPAMP element.

Original languageEnglish
Pages (from-to)256-262
Number of pages7
JournalBlood
Volume104
Issue number1
DOIs
Publication statusPublished - Jul 1 2004

Fingerprint

Mitogen-Activated Protein Kinase Kinases
Transcription
Mitogen-Activated Protein Kinases
Phosphotransferases
Genes
Phosphorylation
Mitogen-Activated Protein Kinase 1
Sp1 Transcription Factor
Urokinase-Type Plasminogen Activator
Heat-Shock Proteins
HeLa Cells
Gene expression
Protein Kinases
Prostate
Adenocarcinoma
Chemical activation
Derivatives
Gene Expression

ASJC Scopus subject areas

  • Hematology

Cite this

MAPK and JNK transduction pathways can phosphorylate Sp1 to activate the uPA minimal promoter element and endogenous gene transcription. / Benasciutti, Elisa; Pagès, Gilles; Kenzior, Olga; Folk, William; Blasi, Francesco; Crippa, Massimo P.

In: Blood, Vol. 104, No. 1, 01.07.2004, p. 256-262.

Research output: Contribution to journalArticle

Benasciutti, Elisa ; Pagès, Gilles ; Kenzior, Olga ; Folk, William ; Blasi, Francesco ; Crippa, Massimo P. / MAPK and JNK transduction pathways can phosphorylate Sp1 to activate the uPA minimal promoter element and endogenous gene transcription. In: Blood. 2004 ; Vol. 104, No. 1. pp. 256-262.
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