Abstract
The p53 protein contains several functional domains necessary for inducing cell cycle arrest and apoptosis. The C-terminal basic domain within residues 364-393 and the proline-rich domain within residues 64-91 are required for apoptotic activity. In addition, activation domain 2 within residues 43-63 is necessary for apoptotic activity when the N-terminal activation domain 1 within residues 1-42 is deleted (ΔAD1) or mutated (AD1-). Here we have discovered that an activation domain 2 mutation at residues 53-54 (AD2-) abrogates the apoptotic activity but has no significant effect on cell cycle arrest. We have also found that p53-(ΔAD2), which lacks activation domain 2, is inert in inducing apoptosis. p53-(AD2-ΔBD), which is defective in activation domain 2 and lacks the C-terminal basic domain, p53-(ΔAD2ΔBD), which lacks both activation domain 2 and the C-terminal basic domain, and p53-(ΔPRDΔBD), which lacks both the proline-rich domain and the C-terminal basic domain, are also inert in inducing apoptosis. All four mutants are still capable of inducing cell cycle arrest, albeit to a lesser extent than wild-type p53. Interestingly, we have found that deletion of the N-terminal activation domain 1 alleviates the requirement of the C-terminal basic domain for apoptotic activity. Thus, we have generated a small but potent p53-(ΔAD1ΔBD) molecule. Furthermore, we have determined that at least two of the three domains (activation domain 1, activation domain 2, and the proline-rich domain), are required for inducing cell cycle arrest. Taken together, our results suggest that activation domain 2 and the proline-rich domain form an activation domain for inducing pro-apoptotic genes or inhibiting anti-apoptotic genes. The C-terminal basic domain is required for maintaining this activation domain competent for transactivation or transrepression.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 39927-39934 |
| Number of pages | 8 |
| Journal | Journal of Biological Chemistry |
| Volume | 275 |
| Issue number | 51 |
| DOIs | |
| State | Published - Dec 22 2000 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Biochemistry
Cite this
Definition of the p53 functional domains necessary for inducing apoptosis. / Zhu, Jianhui; Zhang, Shunzhen; Jiang, Jieyuan; Chen, Xinbin.
In: Journal of Biological Chemistry, Vol. 275, No. 51, 22.12.2000, p. 39927-39934.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Definition of the p53 functional domains necessary for inducing apoptosis
AU - Zhu, Jianhui
AU - Zhang, Shunzhen
AU - Jiang, Jieyuan
AU - Chen, Xinbin
PY - 2000/12/22
Y1 - 2000/12/22
N2 - The p53 protein contains several functional domains necessary for inducing cell cycle arrest and apoptosis. The C-terminal basic domain within residues 364-393 and the proline-rich domain within residues 64-91 are required for apoptotic activity. In addition, activation domain 2 within residues 43-63 is necessary for apoptotic activity when the N-terminal activation domain 1 within residues 1-42 is deleted (ΔAD1) or mutated (AD1-). Here we have discovered that an activation domain 2 mutation at residues 53-54 (AD2-) abrogates the apoptotic activity but has no significant effect on cell cycle arrest. We have also found that p53-(ΔAD2), which lacks activation domain 2, is inert in inducing apoptosis. p53-(AD2-ΔBD), which is defective in activation domain 2 and lacks the C-terminal basic domain, p53-(ΔAD2ΔBD), which lacks both activation domain 2 and the C-terminal basic domain, and p53-(ΔPRDΔBD), which lacks both the proline-rich domain and the C-terminal basic domain, are also inert in inducing apoptosis. All four mutants are still capable of inducing cell cycle arrest, albeit to a lesser extent than wild-type p53. Interestingly, we have found that deletion of the N-terminal activation domain 1 alleviates the requirement of the C-terminal basic domain for apoptotic activity. Thus, we have generated a small but potent p53-(ΔAD1ΔBD) molecule. Furthermore, we have determined that at least two of the three domains (activation domain 1, activation domain 2, and the proline-rich domain), are required for inducing cell cycle arrest. Taken together, our results suggest that activation domain 2 and the proline-rich domain form an activation domain for inducing pro-apoptotic genes or inhibiting anti-apoptotic genes. The C-terminal basic domain is required for maintaining this activation domain competent for transactivation or transrepression.
AB - The p53 protein contains several functional domains necessary for inducing cell cycle arrest and apoptosis. The C-terminal basic domain within residues 364-393 and the proline-rich domain within residues 64-91 are required for apoptotic activity. In addition, activation domain 2 within residues 43-63 is necessary for apoptotic activity when the N-terminal activation domain 1 within residues 1-42 is deleted (ΔAD1) or mutated (AD1-). Here we have discovered that an activation domain 2 mutation at residues 53-54 (AD2-) abrogates the apoptotic activity but has no significant effect on cell cycle arrest. We have also found that p53-(ΔAD2), which lacks activation domain 2, is inert in inducing apoptosis. p53-(AD2-ΔBD), which is defective in activation domain 2 and lacks the C-terminal basic domain, p53-(ΔAD2ΔBD), which lacks both activation domain 2 and the C-terminal basic domain, and p53-(ΔPRDΔBD), which lacks both the proline-rich domain and the C-terminal basic domain, are also inert in inducing apoptosis. All four mutants are still capable of inducing cell cycle arrest, albeit to a lesser extent than wild-type p53. Interestingly, we have found that deletion of the N-terminal activation domain 1 alleviates the requirement of the C-terminal basic domain for apoptotic activity. Thus, we have generated a small but potent p53-(ΔAD1ΔBD) molecule. Furthermore, we have determined that at least two of the three domains (activation domain 1, activation domain 2, and the proline-rich domain), are required for inducing cell cycle arrest. Taken together, our results suggest that activation domain 2 and the proline-rich domain form an activation domain for inducing pro-apoptotic genes or inhibiting anti-apoptotic genes. The C-terminal basic domain is required for maintaining this activation domain competent for transactivation or transrepression.
UR - http://www.scopus.com/inward/record.url?scp=0034704151&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034704151&partnerID=8YFLogxK
U2 - 10.1074/jbc.M005676200
DO - 10.1074/jbc.M005676200
M3 - Article
C2 - 10982799
AN - SCOPUS:0034704151
VL - 275
SP - 39927
EP - 39934
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 51
ER -