Regulation of HDM2 activity by the ribosomal protein L11.
The HDM2 protein plays an important role in regulating the stability and function of the p53 tumor suppressor protein. In this report, we show that the ribosomal protein L11 can interact with HDM2 and inhibit HDM2 function, thus leading to the stabilization and activation of p53. The inhibition of HDM2 activity by L11 shows some similarity to the previously described activity of ARF, and expression of either ARF or L11 can induce a p53 response. Enhancement of the interaction between endogenous L11 and HDM2 following treatment of cells with low levels of actinomycin-D suggests that the HDM2/L11 interaction represents a novel pathway for p53 stabilization in response to perturbations in ribosome biogenesis.
Lohrum
Marion A E
MA
Regulation of Cell Growth Laboratory, NCI-FRCDC, Frederick, MD 21702, USA.
Ludwig
Robert L
RL
Kubbutat
Michael H G
MH
Hanlon
Mary
M
Vousden
Karen H
KH
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002478:Cells, Cultured; D003609:Dactinomycin / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins; D010957:Plasmids; D014176:Protein Biosynthesis; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D021381:Protein Transport; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051736:Proto-Oncogene Proteins c-mdm2; D012269:Ribosomal Proteins / Q000378:metabolism*; D012441:Saccharomyces cerevisiae; D013347:Subcellular Fractions; D025803:Tumor Suppressor Protein p14ARF / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011500:Protein Synthesis Inhibitors; D011518:Proto-Oncogene Proteins; D012269:Ribosomal Proteins; D025803:Tumor Suppressor Protein p14ARF; D016159:Tumor Suppressor Protein p53; C027624:ribosomal protein L11; D003609:Dactinomycin; C497206:MDM2 protein, human; C497207:Mdm2 protein, mouse; D051736:Proto-Oncogene Proteins c-mdm2