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In Vitro Ubiquitination and Deubiquitination Assays of Nucleosomal Histones
Published on: July 25, 2019
AP-1 repressor protein JDP-2: inhibition of UV-mediated apoptosis through p53 down-regulation
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
Abstract:
Members of the AP-1 transcription factor family, especially c-Jun and c-Fos, have long been known to mediate critical steps in the cellular response to ultraviolet (UV) irradiation. We sought to examine whether two newly discovered members of the AP-1 family, JDP-1 and JDP-2, also participate in the mammalian UV response. Here we report that JDP-2, but not JDP-1, is transiently induced upon UV challenge and that elevated levels of JDP-2 increase cell survival following UV exposure. This protective function of JDP-2 appears to be mediated through repression of p53 expression at the transcriptional level, via a conserved atypical AP-1 site in the p53 promoter.
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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