AP-1 repressor protein JDP-2: inhibition of UV-mediated apoptosis through p53 down-regulation

F Piu1, A Aronheim, S Katz

  • 1Department of Pharmacology, Laboratory of Gene Regulation and Signal Transduction, , University of California at San Diego, La Jolla, California 92093-0636, USA. fpiu@acadia-pharm.com

Insights

Jun dimerization partner (JDP)-2, a novel AP-1 transcription factor, enhances cell survival after UV radiation by suppressing p53 expression. JDP-2 is induced by UV exposure, unlike JDP-1.

Area of Science:

  • Molecular biology
  • Cellular response to DNA damage
  • Transcription factors

Background:

  • Activating Protein-1 (AP-1) transcription factors, including c-Jun and c-Fos, are crucial for cellular responses to ultraviolet (UV) irradiation.
  • The AP-1 family has recently expanded with the discovery of new members, such as Jun dimerization partner proteins (JDPs).

Purpose of the Study:

  • To investigate the role of newly identified AP-1 family members, JDP-1 and JDP-2, in the mammalian cellular response to UV irradiation.
  • To determine if JDP-1 or JDP-2 are involved in the UV response pathway.

Main Methods:

  • Quantitative analysis of JDP-1 and JDP-2 expression following UV exposure in mammalian cells.
  • Assessment of cell survival rates after UV irradiation under conditions of varying JDP-2 levels.
  • Investigation of the transcriptional regulation of p53 by JDP-2, including analysis of the p53 promoter.

Main Results:

  • JDP-2, but not JDP-1, demonstrated transient induction in response to UV challenge.
  • Elevated JDP-2 levels were correlated with increased cell survival following UV exposure.
  • JDP-2 was found to repress p53 expression transcriptionally, utilizing an atypical AP-1 binding site within the p53 promoter.

Conclusions:

  • JDP-2 plays a significant role in the mammalian UV response pathway, promoting cell survival.
  • The protective mechanism of JDP-2 involves the transcriptional repression of the tumor suppressor p53.
  • These findings highlight JDP-2 as a key mediator in cellular adaptation to UV-induced DNA damage.

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