Overexpression of SCYL1-BP1 stabilizes functional p53 by suppressing MDM2-mediated ubiquitination.
Previously, we defined SCY1-like 1 binding protein 1 (SCYL1-BP1) to be a substrate of Pirh2 that binds to mouse double minute gene number 2 (MDM2). In the current study, we found that an increase in SCYL1-BP1 protein levels caused a parallel change in the amount of p53 protein due to the inhibition by SCYL-BP1 of MDM2-mediated p53 ubiquitination. SCYL1-BP1 was not able to alter the ubiquitination of p53 by human papillomavirus protein E6, indicating that the effect was specific for MDM2. Increases in the level of SCYL1-BP1 protein in cells led to the greater transcriptional activation of p21 and gadd45, reduced rate of cellular proliferation, increased levels of apoptosis and inhibition of tumorigenicity. Thus, we propose that SCYL1-BP1 is a novel regulator of the MDM2-p53 feedback loop and that it may be a potential tumor suppressor.
Yan
Jing
J
State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, China.
Di
Yujun
Y
Shi
Huili
H
Rao
Hai
H
Huo
Keke
K
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002478:Cells, Cultured; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D000077614:Golgi Matrix Proteins; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008819:Mice, Nude; D055550:Protein Stability; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014183:Transplantation, Heterologous; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination; D000097642:GADD45 Proteins
D002352:Carrier Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D000077614:Golgi Matrix Proteins; D049452:Green Fluorescent Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008156:Luciferases; D051736:Proto-Oncogene Proteins c-mdm2; D016159:Tumor Suppressor Protein p53; D000097642:GADD45 Proteins; C533680:GORAB protein, human