title: Pierce1, a novel p53 target gene contributing to the ultraviolet-induced DNA damage response.
abstract: Retinoblastoma (Rb) and p53 genes are mutated or inactivated in most human cancers and mutually regulate each other. Recently, we reported that expression of diverse genes was altered in Rb-deficient mouse embryonic fibroblasts (MEF). In this study, we found that Pierce1, a novel transcript upregulated in Rb-deficient MEFs, is a transcriptional target of p53. Although Pierce1 promoter did not respond to the ectopic expression of E2F1, it was strongly activated by p53 via 2 cis-elements. Consistently, the expression of Pierce1 was induced by genotoxic stresses that activate p53 but was not detected in p53-deficient MEFs. Pierce1 was posttranslationally stabilized by ultraviolet C (UVC) irradiation, and UVC-activated ATR (ataxia telangiectasia-mutated and Rad3-related) signaling suppressed proteosomal degradation of Pierce1 protein. Furthermore, knockdown of Pierce1 compromised the checkpoint response of wild-type MEFs to UVC irradiation, accompanying the diminished expression of p53 target genes. Together, our data suggest that Pierce1 is an important p53 target gene contributing to normal DNA damage response and may play crucial roles in maintaining genomic integrity against genotoxic stresses, including UVC irradiation.
authors.affiliation: Department of Biochemistry, College of Life Science and Biotechnology, and Laboratory Animal Research Center, Yonsei University, Seoul, Korea.
authors.forename: Young Hoon
authors.initials: YH
authors.lastname: Sung
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Kim
authors.forename: Sushil
authors.initials: S
authors.lastname: Devkota
authors.forename: Jusik
authors.initials: J
authors.lastname: Roh
authors.forename: Jaehoon
authors.initials: J
authors.lastname: Lee
authors.forename: Kunsoo
authors.initials: K
authors.lastname: Rhee
authors.forename: Young Yil
authors.initials: YY
authors.lastname: Bahk
authors.forename: Han-Woong
authors.initials: HW
authors.lastname: Lee
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis / Q000235:genetics; D004249:DNA Damage / Q000235:genetics*; D050687:E2F1 Transcription Factor / Q000235:genetics; D005347:Fibroblasts / Q000502:physiology / Q000528:radiation effects; D005786:Gene Expression Regulation; D016161:Genes, Retinoblastoma; D019942:Genes, p16; D016158:Genes, p53; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D041681:NIH 3T3 Cells; D016160:Retinoblastoma Protein / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D014162:Transfection; D014466:Ultraviolet Rays
chemical_list: C493957:Cdkn1a protein, mouse; C417743:Cdkn2a protein, mouse; D018797:Cell Cycle Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050687:E2F1 Transcription Factor; C493754:E2f1 protein, mouse; D016160:Retinoblastoma Protein