Abstract
p73, a p53 family member, is highly similar to p53 in both structure and function. Like p53, the p73 protein contains an N-terminal activation domain, a DNA-binding domain, a tetramerization domain, and several PXXP motifs. Previously, we and others have shown that some functional domains in p53, such as the DNA-binding and tetramerization domains, are required for inducing both cell cycle arrest and apoptosis whereas others, such as the second activation domain, the proline-rich domain, and the C-terminal basic domain, are only required for inducing apoptosis. To determine the activity of p73 functional domains, we have generated stable inducible cell lines that express p73β and various mutants deficient in one or more functional domains. We found that in addition to the DNA-binding domain, p73-mediated growth suppression requires the N-terminal activation domain and the tetramerization domain. However, unlike p53, p73-mediated apoptosis does not require the region adjacent to the activation domain or the entire C-terminal region. Interestingly, while the N- or the C-terminal PXXP motifs are dispensable for p73 function, deletion of both the N-and the C-terminal PXXP motifs renders p73 inactive in transactivation. In addition, we found that substitution of two conserved tandem hydrophobic residues with two hydrophilic ones, which can abrogate the activity of the first activation domain in p53, has no effect on p73 transcriptional activity. Together, we showed that the p73 protein has its own unique determinants for transactivation and growth suppression.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 4333-4347 |
| Number of pages | 15 |
| Journal | Oncogene |
| Volume | 22 |
| Issue number | 28 |
| DOIs | |
| State | Published - Jul 10 2003 |
| Externally published | Yes |
Fingerprint
Keywords
- Apoptosis
- Cell cycle
- p53 family
- p73
ASJC Scopus subject areas
- Molecular Biology
- Cancer Research
- Genetics
Cite this
Characterization of p73 functional domains necessary for transactivation and growth suppression. / Nozell, Susan; Wu, Yijun; McNaughton, Kelly; Liu, Gang; Willis, Amy; Paik, Jason C.; Chen, Xinbin.
In: Oncogene, Vol. 22, No. 28, 10.07.2003, p. 4333-4347.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Characterization of p73 functional domains necessary for transactivation and growth suppression
AU - Nozell, Susan
AU - Wu, Yijun
AU - McNaughton, Kelly
AU - Liu, Gang
AU - Willis, Amy
AU - Paik, Jason C.
AU - Chen, Xinbin
PY - 2003/7/10
Y1 - 2003/7/10
N2 - p73, a p53 family member, is highly similar to p53 in both structure and function. Like p53, the p73 protein contains an N-terminal activation domain, a DNA-binding domain, a tetramerization domain, and several PXXP motifs. Previously, we and others have shown that some functional domains in p53, such as the DNA-binding and tetramerization domains, are required for inducing both cell cycle arrest and apoptosis whereas others, such as the second activation domain, the proline-rich domain, and the C-terminal basic domain, are only required for inducing apoptosis. To determine the activity of p73 functional domains, we have generated stable inducible cell lines that express p73β and various mutants deficient in one or more functional domains. We found that in addition to the DNA-binding domain, p73-mediated growth suppression requires the N-terminal activation domain and the tetramerization domain. However, unlike p53, p73-mediated apoptosis does not require the region adjacent to the activation domain or the entire C-terminal region. Interestingly, while the N- or the C-terminal PXXP motifs are dispensable for p73 function, deletion of both the N-and the C-terminal PXXP motifs renders p73 inactive in transactivation. In addition, we found that substitution of two conserved tandem hydrophobic residues with two hydrophilic ones, which can abrogate the activity of the first activation domain in p53, has no effect on p73 transcriptional activity. Together, we showed that the p73 protein has its own unique determinants for transactivation and growth suppression.
AB - p73, a p53 family member, is highly similar to p53 in both structure and function. Like p53, the p73 protein contains an N-terminal activation domain, a DNA-binding domain, a tetramerization domain, and several PXXP motifs. Previously, we and others have shown that some functional domains in p53, such as the DNA-binding and tetramerization domains, are required for inducing both cell cycle arrest and apoptosis whereas others, such as the second activation domain, the proline-rich domain, and the C-terminal basic domain, are only required for inducing apoptosis. To determine the activity of p73 functional domains, we have generated stable inducible cell lines that express p73β and various mutants deficient in one or more functional domains. We found that in addition to the DNA-binding domain, p73-mediated growth suppression requires the N-terminal activation domain and the tetramerization domain. However, unlike p53, p73-mediated apoptosis does not require the region adjacent to the activation domain or the entire C-terminal region. Interestingly, while the N- or the C-terminal PXXP motifs are dispensable for p73 function, deletion of both the N-and the C-terminal PXXP motifs renders p73 inactive in transactivation. In addition, we found that substitution of two conserved tandem hydrophobic residues with two hydrophilic ones, which can abrogate the activity of the first activation domain in p53, has no effect on p73 transcriptional activity. Together, we showed that the p73 protein has its own unique determinants for transactivation and growth suppression.
KW - Apoptosis
KW - Cell cycle
KW - p53 family
KW - p73
UR - http://www.scopus.com/inward/record.url?scp=0041302159&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0041302159&partnerID=8YFLogxK
U2 - 10.1038/sj.onc.1206470
DO - 10.1038/sj.onc.1206470
M3 - Article
VL - 22
SP - 4333
EP - 4347
JO - Oncogene
JF - Oncogene
SN - 0950-9232
IS - 28
ER -