Identification and characterization of early growth response 2, a zinc-finger transcription factor, as a p53-regulated proapoptotic gene.
Tumor suppressor p53 is a transcription factor that induces growth arrest and/or apoptosis in response to cellular stress. In recent years, many genes have been identified as p53-regulated genes; however, no single target gene has been shown to be required for the apoptotic effect. Using microarray analysis, we have identified the transcription factor early growth response 2 (EGR2) as a target of the p53 family, specifically p53, p63 and p73. EGR2 expression was up-regulated by DNA damage-induced p53 activity, as well as by overexpression of p53 family genes. Furthermore, we identified a responsive element to p53, TAp63, and TAp73 within the EGR2 gene. This response element is highly conserved between human and rodents. We also found that overexpression of EGR2 induced apoptosis when combined with anticancer agents. Conversely, inactivation of EGR2 attenuated p53-mediated apoptosis. The results presented here suggest that EGR2 is a direct transcriptional target of p53 family that can in part mediate the p53-dependent apoptotic pathway.
Department of Molecular Biology, Cancer Research Institute, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo 060-8556, Japan.
Ikuko
I
Yokota
Yasushi
Y
Sasaki
Lisa
L
Kashima
Masashi
M
Idogawa
Takashi
T
Tokino
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D001483:Base Sequence; D002478:Cells, Cultured; D051767:Early Growth Response Protein 2 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D045325:HCT116 Cells; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D016335:Zinc Fingers / Q000235:genetics
D051767:Early Growth Response Protein 2; D034741:RNA, Small Interfering; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53