title: Transactivation of the EGR1 gene contributes to mutant p53 gain of function.
abstract: Tumor-associated mutants of the p53 tumor suppressor protein exert biological activities compatible with an oncogenic gain of function. To explore the underlying molecular mechanism, we performed microarray analysis, comparing p53-null cells to mutant p53-expressing cells. One of the genes up-regulated in the presence of mutant p53 was EGR1, a transcription factor implicated in growth control, apoptosis, and cancer. EGR1 induction by various types of stress is markedly augmented in cells expressing mutant p53. Moreover, chromatin immunoprecipitation analysis indicates that mutant p53 is physically associated with the EGR1 promoter. Functional assays indicate that induction of EGR1 by mutant p53 contributes to enhanced transformed properties and resistance to apoptosis. We propose that EGR1 is a significant contributor to mutant p53 gain of function.
authors.affiliation: Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Lilach
authors.initials: L
authors.lastname: Weisz
authors.forename: Amir
authors.initials: A
authors.lastname: Zalcenstein
authors.forename: Perry
authors.initials: P
authors.lastname: Stambolsky
authors.forename: Yehudit
authors.initials: Y
authors.lastname: Cohen
authors.forename: Naomi
authors.initials: N
authors.lastname: Goldfinger
authors.forename: Moshe
authors.initials: M
authors.lastname: Oren
authors.forename: Varda
authors.initials: V
authors.lastname: Rotter
mesh_terms: D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics*; D051766:Early Growth Response Protein 1; D016158:Genes, p53; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics*; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics*; D015533:Transcriptional Activation / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D017931:DNA Primers; D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D017874:Immediate-Early Proteins; D014157:Transcription Factors