Ribosomal protein S7 is both a regulator and a substrate of MDM2.
MDM2 associates with ribosomal protein S7, and this interaction is required to inhibit MDM2's E3 ligase activity, leading to stabilization of MDM2 and p53. Notably, the MDM2 homolog MDMX facilitates the inhibition of MDM2 E3 ligase activity by S7. Further, ablation of S7 inhibits MDM2 and p53 accumulation induced by different stress signals in some cell types. Thus, ribosomal/nucleolar stress is likely a key integrating event in DNA damage signaling to p53. Interestingly, S7 is itself a substrate for MDM2 E3 ligase activity both in vitro and in vivo. An S7-ubiquitin fusion protein (S7-Ub) selectively inhibits MDM2 degradation of p53 and is unaffected by MDMX. S7-Ub promotes apoptosis to a greater extent than S7 alone. This indicates that MDM2 ubiquitination of S7 is involved in sustaining the p53 response. Thus, S7 functions as both effector and affector of MDM2 to ensure a proper cellular response to different stress signals.
Zhu
Yan
Y
Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
Poyurovsky
Masha V
MV
Li
Yingchun
Y
Biderman
Lynn
L
Stahl
Joachim
J
Jacq
Xavier
X
Prives
Carol
C
D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D015536:Down-Regulation; D006801:Humans; D051379:Mice; D025941:Protein Interaction Mapping; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics / Q000378:metabolism*; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D013312:Stress, Physiological; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D054875:Ubiquitination
D012269:Ribosomal Proteins; D016159:Tumor Suppressor Protein p53; C037442:ribosomal protein S7; D051736:Proto-Oncogene Proteins c-mdm2
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