Abstract
AIMP2/p38 is a scaffolding protein required for the assembly of the macromolecular tRNA synthetase complex. Here, we describe a previously unknown function for AIMP2 as a positive regulator of p53 in response to genotoxic stresses. Depletion of AIMP2 increased resistance to DNA damage-induced apoptosis, and introduction of AIMP2 into AIMP2-deficient cells restored the susceptibility to apoptosis. Upon DNA damage, AIMP2 was phosphorylated, dissociated from the multi-tRNA synthetase complex, and translocated into the nuclei of cells. AIMP2 directly interacts with p53, thereby preventing MDM2-mediated ubiquitination and degradation of p53. Mutations in AIMP2, affecting its interaction with p53, hampered its ability to activate p53. Nutlin-3 recovered the level of p53 and the susceptibility to UV-induced cell death in AIMP2-deficient cells. This work demonstrates that AIMP2, a component of the translational machinery, functions as proapoptotic factor via p53 in response to DNA damage.
| Original language | English |
|---|---|
| Pages (from-to) | 11206-11211 |
| Number of pages | 6 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 105 |
| Issue number | 32 |
| DOIs | |
| Publication status | Published - 2008 Aug 12 |
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AIMP2/p38, the scaffold for the multi-tRNA synthetase complex, responds to genotoxic stresses via p53. / Jung, Min Han; Park, Bum Joon; Sang, Gyu Park; Young, Sun Oh; So, Jung Choi; Sang, Won Lee; Hwang, Soon Kyung; Chang, Seung Hee; Cho, Myung Haing; Kim, Sunghoon.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 105, No. 32, 12.08.2008, p. 11206-11211.Research output: Contribution to journal › Article
TY - JOUR
T1 - AIMP2/p38, the scaffold for the multi-tRNA synthetase complex, responds to genotoxic stresses via p53
AU - Jung, Min Han
AU - Park, Bum Joon
AU - Sang, Gyu Park
AU - Young, Sun Oh
AU - So, Jung Choi
AU - Sang, Won Lee
AU - Hwang, Soon Kyung
AU - Chang, Seung Hee
AU - Cho, Myung Haing
AU - Kim, Sunghoon
PY - 2008/8/12
Y1 - 2008/8/12
N2 - AIMP2/p38 is a scaffolding protein required for the assembly of the macromolecular tRNA synthetase complex. Here, we describe a previously unknown function for AIMP2 as a positive regulator of p53 in response to genotoxic stresses. Depletion of AIMP2 increased resistance to DNA damage-induced apoptosis, and introduction of AIMP2 into AIMP2-deficient cells restored the susceptibility to apoptosis. Upon DNA damage, AIMP2 was phosphorylated, dissociated from the multi-tRNA synthetase complex, and translocated into the nuclei of cells. AIMP2 directly interacts with p53, thereby preventing MDM2-mediated ubiquitination and degradation of p53. Mutations in AIMP2, affecting its interaction with p53, hampered its ability to activate p53. Nutlin-3 recovered the level of p53 and the susceptibility to UV-induced cell death in AIMP2-deficient cells. This work demonstrates that AIMP2, a component of the translational machinery, functions as proapoptotic factor via p53 in response to DNA damage.
AB - AIMP2/p38 is a scaffolding protein required for the assembly of the macromolecular tRNA synthetase complex. Here, we describe a previously unknown function for AIMP2 as a positive regulator of p53 in response to genotoxic stresses. Depletion of AIMP2 increased resistance to DNA damage-induced apoptosis, and introduction of AIMP2 into AIMP2-deficient cells restored the susceptibility to apoptosis. Upon DNA damage, AIMP2 was phosphorylated, dissociated from the multi-tRNA synthetase complex, and translocated into the nuclei of cells. AIMP2 directly interacts with p53, thereby preventing MDM2-mediated ubiquitination and degradation of p53. Mutations in AIMP2, affecting its interaction with p53, hampered its ability to activate p53. Nutlin-3 recovered the level of p53 and the susceptibility to UV-induced cell death in AIMP2-deficient cells. This work demonstrates that AIMP2, a component of the translational machinery, functions as proapoptotic factor via p53 in response to DNA damage.
UR - http://www.scopus.com/inward/record.url?scp=49649116700&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=49649116700&partnerID=8YFLogxK
U2 - 10.1073/pnas.0800297105
DO - 10.1073/pnas.0800297105
M3 - Article
C2 - 18695251
AN - SCOPUS:49649116700
VL - 105
SP - 11206
EP - 11211
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 - 32
ER -