Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 9614-9619 |
| Number of pages | 6 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 107 |
| Issue number | 21 |
| DOIs | |
| State | Published - May 25 2010 |
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Keywords
- mRNA stability
- p63
- RBM38
- RNPC1
- The p53 family
ASJC Scopus subject areas
- General
Cite this
RNPC1, an RNA-binding protein and a target of the p53 family, regulates p63 expression through mRNA stability. / Zhang, Jin; Cho, Seong Jun; Chen, Xinbin.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 107, No. 21, 25.05.2010, p. 9614-9619.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - RNPC1, an RNA-binding protein and a target of the p53 family, regulates p63 expression through mRNA stability
AU - Zhang, Jin
AU - Cho, Seong Jun
AU - Chen, Xinbin
PY - 2010/5/25
Y1 - 2010/5/25
N2 - 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.
AB - 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.
KW - mRNA stability
KW - p63
KW - RBM38
KW - RNPC1
KW - The p53 family
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U2 - 10.1073/pnas.0912594107
DO - 10.1073/pnas.0912594107
M3 - Article
VL - 107
SP - 9614
EP - 9619
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 21
ER -