Tissue-specific expression of p73 C-terminal isoforms in mice

被引:27
|
作者
Grespi, Francesca [1 ,2 ,3 ]
Amelio, Ivano [1 ,2 ,3 ]
Tucci, Paola [1 ,4 ]
Annicchiarico-Petruzzelli, Margherita [5 ,6 ]
Melino, Gerry [1 ,2 ,3 ,5 ,6 ]
机构
[1] Univ Leicester, MRC, Toxicol Unit, Leicester, Leics, England
[2] Univ Ghent VIB, Dept Mol Biomed Res, Ghent, Belgium
[3] Univ Ghent, Dept Biomed Mol Biol, B-9000 Ghent, Belgium
[4] Univ Calabria, Dept Pharmacobiol, I-87036 Cosenza, Italy
[5] Univ Roma Tor Vergata, Biochem IDI IRCCS Lab, Rome, Italy
[6] Univ Roma Tor Vergata, Dept Expt Med & Surg, Rome, Italy
基金
英国医学研究理事会;
关键词
p73; C-terminal isoforms; SAM domain; cancer; development; STERILE-ALPHA-MOTIF; P53; FAMILY-MEMBERS; DNA-DAMAGE; NEURONAL DIFFERENTIATION; SAM DOMAIN; CARCINOMA CELLS; IN-VITRO; P63; INDUCTION; APOPTOSIS;
D O I
10.4161/cc.22787
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 Delta Np73, 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. Delta Np73-selective knockout, on the other hand, highlights anti-apoptotic function of Delta Np73 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.
引用
收藏
页码:4474 / 4483
页数:10
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