Ribosomal protein L23 activates p53 by inhibiting MDM2 function in response to ribosomal perturbation but not to translation inhibition.
The p53-MDM2 feedback loop is vital for cell growth control and is subjected to multiple regulations in response to various stress signals. Here we report another regulator of this loop. Using an immunoaffinity method, we purified an MDM2-associated protein complex that contains the ribosomal protein L23. L23 interacted with MDM2, forming a complex independent of the 80S ribosome and polysome. The interaction of L23 with MDM2 was enhanced by treatment with actinomycin D but not by gamma-irradiation, leading to p53 activation. This activation was inhibited by small interfering RNA against L23. Ectopic expression of L23 reduced MDM2-mediated p53 ubiquitination and also induced p53 activity and G(1) arrest in p53-proficient U2OS cells but not in p53-deficient Saos-2 cells. These results reveal that L23 is another regulator of the p53-MDM2 feedback regulation.
Department of Biochemistry and Molecular Biology, Oregon Health and Science University, 3181 SW Sam Jackson Park Rd., Portland, OR 97201, USA.
Mu-Shui
MS
Dai
Shelya X
SX
Zeng
Yetao
Y
Jin
Xiao-Xin
XX
Sun
Larry
L
David
Hua
H
Lu
D000595:Amino Acid Sequence; D002453:Cell Cycle / Q000502:physiology; D002460:Cell Line; D003609:Dactinomycin / Q000378:metabolism; D005720:Gamma Rays; D006801:Humans; D046911:Macromolecular Substances; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D014176:Protein Biosynthesis; D011500:Protein Synthesis Inhibitors / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051736:Proto-Oncogene Proteins c-mdm2; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D046911:Macromolecular Substances; D009687:Nuclear Proteins; D011500:Protein Synthesis Inhibitors; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D012269:Ribosomal Proteins; D016159:Tumor Suppressor Protein p53; C027624:ribosomal protein L11; C032493:ribosomal protein L17; C029742:ribosomal protein L5; D003609:Dactinomycin; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2