Priority Research Papers:

Cancer-mutated ribosome protein L22 (RPL22/eL22) suppresses cancer cell survival by blocking p53-MDM2 circuit

Bo Cao, Ziling Fang, Peng Liao, Xiang Zhou, Jianping Xiong, Shelya Zeng and Hua Lu _

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Oncotarget. 2017; 8:90651-90661. https://doi.org/10.18632/oncotarget.21544

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Bo Cao1, Ziling Fang1,2, Peng Liao1, Xiang Zhou1,3, Jianping Xiong2, Shelya Zeng1 and Hua Lu1

1 Department of Biochemistry & Molecular Biology, Tulane Cancer Center, Tulane University School of Medicine, New Orleans, LA, USA

2 The First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China

3 Fudan University Shanghai Cancer Center and the Institutes of Biomedical Sciences, Fudan University, Shanghai, People’s Republic of China

Correspondence to:

Hua Lu, email:

Keywords: RPL22/eL22, p53, MDM2, RPL11/uL5, RPL5/uL18

Received: July 25, 2017 Accepted: September 08, 2017 Published: October 06, 2017


Several ribosomal proteins (RPs) in response to various ribosomal stressors have been shown to play a critical role in p53-dependent regulation of cell cycle arrest, apoptosis and tumor suppression. Here, we report ribosomal protein L22 (RPL22/eL22) as a novel p53 activator highly mutated (mostly deletion mutation) in various types of human cancers, but not essential for ribosomal biogenesis in normal cells. Ectopic expression of RPL22/eL22 suppressed the colony formation of cancer cells in a p53-dependent manner, whereas knockdown of RPL22/eL22 significantly compromised p53 activation by Actinomycin D, rescuing p53-induced G1/G0 cell cycle arrest. Interestingly, human tumors with RPL22/eL22 deletion appeared to sustain wild type p53. Mechanistically, RPL22/eL22 bound to MDM2 acidic domain and inhibited MDM2-mediated p53 ubiquitination and degradation, hence extending the half-life of p53. Ribosome-profiling analysis revealed that induction of ribosomal stress by Actinomycin D leads to the increase of ribosome-free RPL22/eL22 pool. Also, RPL22/eL22 formed a complex with MDM2/RPL5/uL18/RPL11/uL5 and synergized with RPL11/uL5 to activate p53. Furthermore, the N terminus of RPL22/eL22 bound to MDM2, while the C terminus interacted with RPL5/uL18/RPL11/uL5; both of these two fragments activated p53 by inhibiting MDM2. Our study indicates that RPL22/eL22 highly mutated in human cancers plays an anti-cancer role likely through regulation of the MDM2-p53 feedback loop, and also suggests that targeting the RPL22/eL22-MDM2-p53 pathway could be a potential strategy for future development of anti-cancer therapy.

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