RNPC1, an RNA-binding protein and a target of the p53 family, regulates p63 expression through mRNA stability.
P63, a p53 family tumor suppressor, is involved in many cellular processes, including growth suppression and differentiation. Thus, p63 activity needs to be tightly controlled. Here, we found that RNPC1, a RNA-binding protein and a target of the p53 family, regulates p63 mRNA stability and consequently p63 activity. Specifically, we showed that overexpression of RNPC1 decreases, whereas knockdown of RNPC1 increases, the half-life of p63 transcript, which leads to altered p63 expression. Consistent with this, we showed that RNPC1 binds the AU-/U-rich elements in p63 3' UTR in vitro and in vivo and the RRM domain in RNPC1 is required for binding, and regulating the stability of, p63 transcript. Furthermore, we showed that RNPC1 promotes keratinocyte differentiation by repressing p63 expression. Together, we uncovered a previously undetected mechanism by which p63 expression is regulated via mRNA stability and a novel regulatory feedback loop between RNPC1 and p63.
Zhang
Jin
J
Comparative Cancer Center, University of California, Davis, CA 95616, USA.
Jun Cho
Seong
S
Chen
Xinbin
X
D020413:3' Untranslated Regions / Q000235:genetics; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D015536:Down-Regulation; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D020871:RNA Stability; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D020413:3' Untranslated Regions; C081876:CKAP4 protein, human; D008565:Membrane Proteins; C515435:RBM38 protein, human; D016601:RNA-Binding Proteins
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