Journal
CELL DEATH AND DIFFERENTIATION
Volume 14, Issue 3, Pages 436-446Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.cdd.4402029
Keywords
Egr1; p73; p53; transcription regulation; feedback loops; chromatin immunoprecipitation; Egr1 knockout mice
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Funding
- NCI NIH HHS [R01 CA67888, R01 CA76173, R01 CA102688, R01 CA96949] Funding Source: Medline
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p73, a transcription factor rarely mutated in cancer, regulates a subset of p53 target genes that cause cells to respond to genotoxic stress by growth arrest and apoptosis. p73 is produced in two main forms; only TAp73 reiterates the roles of p53, while Delta Np73 can be oncogenic in character. We show that the TAp73 form produced by TP73 P1 promoter has five distinct Egr1-binding sites, each contributing to the transcriptional upregulation of TAp73 by Egr1 in several cell types. In contrast, TP73 P2 promoter transcribes DNp73, is not induced by Egr1, but is induced by TAp73 and p53. Induction of TAp73 by genotoxic stress requires Egr1 in mouse in vivo. Newly discovered non-consensus p53-binding sites in p73, p53 and Egr1 promoters reveal interregulating networks and sustained expression by feedback loops in response to stress, resulting in prolonged expression of the p53 family of genes and efficient apoptosis.
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