The p53 target Wig-1 regulates p53 mRNA stability through an AU-rich element.
The p53 target gene Wig-1 encodes a double-stranded-RNA-binding zinc finger protein. We show here that Wig-1 binds to p53 mRNA and stabilizes it through an AU-rich element (ARE) in the 3' UTR of the p53 mRNA. This effect is mirrored by enhanced p53 protein levels in both unstressed cells and cells exposed to p53-activating stress agents. Thus, the p53 target Wig-1 is a previously undescribed ARE-regulating protein that acts as a positive feedback regulator of p53, with implications both for the steady-state levels of p53 and for the p53 stress response. Our data reveal a previously undescribed link between the tumor suppressor p53 and posttranscriptional gene regulation via AREs in mRNA.
Vilborg
Anna
A
Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska Institute, SE-171 76 Stockholm, Sweden.
Glahder
Jacob A
JA
Wilhelm
Margareta T
MT
Bersani
Cinzia
C
Corcoran
Martin
M
Mahmoudi
Salah
S
Rosenstierne
Maiken
M
Grandér
Dan
D
Farnebo
Marianne
M
Norrild
Bodil
B
Wiman
Klas G
KG
D020413:3' Untranslated Regions; D000818:Animals; D001482:Base Composition; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D025461:Feedback, Physiological; D016158:Genes, p53; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020871:RNA Stability; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D016601:RNA-Binding Proteins; D013312:Stress, Physiological; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D020413:3' Untranslated Regions; D002352:Carrier Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C436503:ZMAT3 protein, human