Ectopic expression of nonliganded retinoic acid receptor β abrogates AP-1 activity by selective degradation of c-Jun in cervical carcinoma cells

Johanna De Castro Arce, Ubaldo Soto, Jan Van Riggelen, Elisabeth Schwarz, Harald Zur Hausen, Frank Rösl

Research output: Contribution to journalArticle

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Abstract

Expression of the nuclear retinoic acid receptor β2 (RARβ2) gene is often disturbed in cervical carcinoma cells. One important mechanism by which RARβ2 can exert growth inhibitory function is based on its ability to repress the AP-1 transcription factor in a ligand-dependent manner. Because less is known about the biological effects of RARβ in the absence of ligand, the corresponding cDNA was stably introduced into HPV18-positive HeLa cervical carcinoma cells. In the present study we describe a novel mechanism by which AP-1 becomes inactivated. Constitutive expression of nonliganded RARβ abrogated both AP-1 binding affinity and activity by a selective degradation of the c-Jun protein as major dimerization partner, without substitution by other members of the Jun family. Blockage of the proteasomal pathway completely rescued c-Jun and reconstituted the AP-1 function. Moreover, HeLa RARβ clones treated either with tumor necrosis factor-α or transfected with a constitutive active upstream mitogen-activated protein kinase (MEKK1Δ) also resulted in c-Jun phosphorylation and restoration of AP-1 affinity and functionality similar to that found in nontransfected parental HeLa cells. These data revealed an important cross-talk between trans-repression of AP-1 and nonliganded RARβ in human papillomavirus-positive cells. Because AP-1 activity was not irreversibly disturbed, but could be switched on through activation of the Jun N-terminal kinase pathway, a model for the transient activation of AP-1 even in the presence of RARβ as repressor is suggested.

Original languageEnglish (US)
Pages (from-to)45408-45416
Number of pages9
JournalJournal of Biological Chemistry
Volume279
Issue number44
DOIs
StatePublished - Oct 29 2004

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Retinoic Acid Receptors
Transcription Factor AP-1
Cells
Carcinoma
Degradation
Chemical activation
Proto-Oncogene Proteins c-jun
Ligands
Phosphorylation
Aptitude
Dimerization
Ectopic Gene Expression
Mitogen-Activated Protein Kinases
HeLa Cells
Restoration
Substitution reactions
Phosphotransferases
Complementary DNA
Clone Cells
Tumor Necrosis Factor-alpha

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Ectopic expression of nonliganded retinoic acid receptor β abrogates AP-1 activity by selective degradation of c-Jun in cervical carcinoma cells. / Arce, Johanna De Castro; Soto, Ubaldo; Van Riggelen, Jan; Schwarz, Elisabeth; Zur Hausen, Harald; Rösl, Frank.

In: Journal of Biological Chemistry, Vol. 279, No. 44, 29.10.2004, p. 45408-45416.

Research output: Contribution to journalArticle

Arce, Johanna De Castro ; Soto, Ubaldo ; Van Riggelen, Jan ; Schwarz, Elisabeth ; Zur Hausen, Harald ; Rösl, Frank. / Ectopic expression of nonliganded retinoic acid receptor β abrogates AP-1 activity by selective degradation of c-Jun in cervical carcinoma cells. In: Journal of Biological Chemistry. 2004 ; Vol. 279, No. 44. pp. 45408-45416.
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