The novel p53 target gene IRF2BP2 participates in cell survival during the p53 stress response.
The tumor suppressor p53 contributes to the cellular fate after genotoxic insults, mainly through the regulation of target genes, thereby allowing e.g. repair mechanisms resulting in cell survival or inducing apoptosis. Unresolved so far is the issue, which exact mechanisms lead to one or the other cellular outcome. Here, we describe the interferon regulatory factor-2-binding protein-2 (IRF2BP2) as a new direct target gene of p53, influencing the p53-mediated cellular decision. We show that upregulation of IRF2BP2 after treatment with actinomycin D (Act.D) is dependent on functional p53 in different cell lines. This occurs in parallel with the down-regulation of the interacting partner of IRF2BP2, the interferon regulatory factor-2 (IRF2), which is known to positively influence cell growth. Analyzing the molecular functions of IRF2BP2, it appears to be able to impede on the p53-mediated transactivation of the p21- and the Bax-gene. We show here that overexpressed IRF2BP2 has an impact on the cellular stress response after Act.D treatment and that it diminishes the induction of apoptosis after doxorubicin treatment. Furthermore, the knockdown of IRF2BP2 leads to an upregulation of p21 and faster induction of apoptosis after doxorubicin as well as Act.D treatment.
Koeppel
Max
M
Department of Molecular Biology, Faculty of Science, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen, Nijmegen, The Netherlands.
van Heeringen
Simon J
SJ
Smeenk
Leonie
L
Navis
Anna C
AC
Janssen-Megens
Eva M
EM
Lohrum
Marion
M
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis; D001665:Binding Sites; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival; D004268:DNA-Binding Proteins; D003609:Dactinomycin / Q000494:pharmacology / Q000633:toxicity; D004317:Doxorubicin / Q000494:pharmacology; D006801:Humans; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D000903:Antibiotics, Antineoplastic; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C475082:IRF2BP2 protein, human; D009687:Nuclear Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D003609:Dactinomycin; D004317:Doxorubicin