TY - JOUR
T1 - Ribosomal protein S2 interplays with MDM2 to induce p53
AU - Cho, Jinhong
AU - Park, Jinyoung
AU - Shin, Sang Chul
AU - Kim, Jae Hong
AU - Kim, Eunice Eun Kyeong
AU - Song, Eun Joo
N1 - Funding Information:
This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIP) (2019R1A2C2004052 and 2017R1A2B3007224) and the R&D Convergence Program of NST (National Research Council of Science & Technology) of Republic of Korea (CAP-16-03-KRIBB).
Funding Information:
This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIP) ( 2019R1A2C2004052 and 2017R1A2B3007224 ) and the R&D Convergence Program of NST (National Research Council of Science & Technology) of Republic of Korea ( CAP-16-03-KRIBB ).
Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/3/5
Y1 - 2020/3/5
N2 - The MDM2-p53 pathway is crucial for maintenance of p53 homeostasis. Some ribosomal proteins (RPs) play critical roles in regulating p53 by interacting with MDM2. However, the role and functional mechanism of each RP in MDM2-p53 pathway still remain unknown. In this study, we found that Ribosomal Protein S2 (RPS2) is a new regulator of MDM2-P53 signaling pathway to regulate p53 protein level. Here, we characterized that RPS2 interacts with MDM2 through the RING finger domain of MDM2. RPS2 is ubiquitinated by MDM2 and the ubiquitinated status of RPS2 regulates the stability of p53, which is activated in response to cellular stresses such as DNA damage, oxidative stress, and especially ribosomal stress. In addition, p53 is not induced in RPS2 knockdown even in the ribosomal stressed condition, indicating that RPS2 is essential for the stabilization of p53. Collectively, our data suggest that RPS2 plays a critical role in the regulation of p53 signaling including the ribosomal stress response.
AB - The MDM2-p53 pathway is crucial for maintenance of p53 homeostasis. Some ribosomal proteins (RPs) play critical roles in regulating p53 by interacting with MDM2. However, the role and functional mechanism of each RP in MDM2-p53 pathway still remain unknown. In this study, we found that Ribosomal Protein S2 (RPS2) is a new regulator of MDM2-P53 signaling pathway to regulate p53 protein level. Here, we characterized that RPS2 interacts with MDM2 through the RING finger domain of MDM2. RPS2 is ubiquitinated by MDM2 and the ubiquitinated status of RPS2 regulates the stability of p53, which is activated in response to cellular stresses such as DNA damage, oxidative stress, and especially ribosomal stress. In addition, p53 is not induced in RPS2 knockdown even in the ribosomal stressed condition, indicating that RPS2 is essential for the stabilization of p53. Collectively, our data suggest that RPS2 plays a critical role in the regulation of p53 signaling including the ribosomal stress response.
KW - MDM2
KW - p53
KW - Ribosomal protein S2
KW - Ubiquitination
UR - http://www.scopus.com/inward/record.url?scp=85077714996&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2020.01.038
DO - 10.1016/j.bbrc.2020.01.038
M3 - Article
C2 - 31928715
AN - SCOPUS:85077714996
SN - 0006-291X
VL - 523
SP - 542
EP - 547
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 2
ER -