title: Tissue-specific expression of p73 C-terminal isoforms in mice.
abstract: p73 is a p53 family transcription factor. Due to the presence in the 5' flanking region of two promoters, there are two N-terminal variants, TAp73, which retains a fully active transactivation domain (TA), and ΔNp73, in which the N terminus is truncated. In addition, extensive 3' splicing gives rise to at least seven distinctive isoforms; TAp73-selective knockout highlights its role as a regulator of cell death, senescence and tumor suppressor. ΔNp73-selective knockout, on the other hand, highlights anti-apoptotic function of ΔNp73 and its involvement in DNA damage response. In this work, we investigated the expression pattern of murine p73 C-terminal isoforms. By using a RT-PCR approach, we were able to detect mRNAs of all the C-terminal isoforms described in humans. We characterized their in vivo expression profile in mouse organs and in different mouse developmental stages. Finally, we investigated p73 C-terminal expression profile following DNA damage, ex vivo after primary cultures treatment and in vivo after systemic administration of cytotoxic compounds. Overall, our study first elucidates spatio-temporal expression of mouse p73 isoforms and provides novel insights on their expression-switch under triggered conditions.
authors.affiliation: Medical Research Council, Toxicology Unit, Leicester University, Leicester, UK.
authors.forename: Francesca
authors.initials: F
authors.lastname: Grespi
authors.forename: Ivano
authors.initials: I
authors.lastname: Amelio
authors.forename: Paola
authors.initials: P
authors.lastname: Tucci
authors.forename: Margherita
authors.initials: M
authors.lastname: Annicchiarico-Petruzzelli
authors.forename: Gerry
authors.initials: G
authors.lastname: Melino
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002478:Cells, Cultured; D002945:Cisplatin / Q000494:pharmacology; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D047108:Embryonic Development; D005047:Etoposide / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D051379:Mice; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; C000606460:TP73 protein, human; C000606368:Trp73 protein, mouse; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; C000606369:delta Np73 protein, human; D005047:Etoposide; D002945:Cisplatin