AP-1 - The Jun proteins: Oncogenes or tumor suppressors in disguise?

Eitan Shaulian*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

348 Scopus citations

Abstract

Since its discovery more than two decades ago the involvement of the Activating protein 1 (AP-1) in proliferation, inflammation, differentiation, apoptosis, cellular migration and wound healing has been intensively studied. A model based on the early studies suggested antagonistic roles for the Jun proteins in proliferation and transformation. c-Jun was suggested to enhance transformation whereas JunB suggested to inhibit it in an antagonistic manner. Surprisingly, despite accumulation of data obtained from animal models regarding the role of Jun proteins in cancer and identification of oncogenic pathways regulating them, their involvement in human cancer was not demonstrated until recently. Here, we will describe the current knowledge about the roles of Jun proteins in human neoplasia. We will focus on the pathological examples demonstrating that the initial dogma has to be reexamined. For example, like c-Jun, JunB seems to play an oncogenic role in lymphomas, particularly in Hodgkin's lympomas. Furthermore, unlike the antagonistic activities of c-Jun and JunB in the transcription of genes coding for major cell cycle regulators such as CyclinD or p16INK4A, the transcription of other cell cycle regulating genes is modified similarly by c-Jun or JunB. Interestingly, some of these genes such as the ones coding for CyclinA or p19ARF are important players in either positive or negative regulation of cellular proliferation and survival. Finally, we will also discuss results posing JNK, known so far as the major activator of c-Jun, as a negative regulator of c-Jun level and activity. These recent findings suggest that the role of each Jun protein in neoplasia as well as in cellular survival should be examined in a context-dependent manner.

Original languageAmerican English
Pages (from-to)894-899
Number of pages6
JournalCellular Signalling
Volume22
Issue number6
DOIs
StatePublished - Jun 2010

Bibliographical note

Funding Information:
I would like to thank Z. Bar Shavit for critical reading. The work in the laboratory of the author is supported by grants from the Israel Science Foundation , the Israel Cancer Research Fund and the Israel Cancer Association .

Keywords

  • AP-1
  • C-Jun
  • Cancer
  • JNK
  • JunB
  • JunD

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