RYBP stabilizes p53 by modulating MDM2.
The mouse double minute 2 (MDM2)-p53 interaction regulates the activity of p53 and is a potential target for human cancer therapy. Here, we report that RYBP (RING1- and YY1-binding protein), a member of the polycomb group (PcG), interacts with MDM2 and decreases MDM2-mediated p53 ubiquitination, leading to stabilization of p53 and an increase in p53 activity. RYBP induces cell-cycle arrest and is involved in the p53 response to DNA damage. Expression of RYBP is decreased in human cancer tissues compared with adjacent normal tissues. These results show that RYBP is a new regulator of the MDM2-p53 loop and that it has tumour suppressor activity.
Chen
Deng
D
Department of Pharmacology and Toxicology, University of Alabama at Birmingham, 1670 University Boulevard, Volker Hall 113, Birmingham, Alabama 35294, USA.
Zhang
Jianbing
J
Li
Mao
M
Rayburn
Elizabeth R
ER
Wang
Hui
H
Zhang
Ruiwen
R
D000818:Animals; D019556:COS Cells; D002453:Cell Cycle / Q000502:physiology; D045744:Cell Line, Tumor / Q000187:drug effects / Q000378:metabolism; D002522:Chlorocebus aethiops; D004249:DNA Damage; D015536:Down-Regulation; D005047:Etoposide / Q000494:pharmacology; D025461:Feedback, Physiological; D016147:Genes, Tumor Suppressor; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D008113:Liver Neoplasms / Q000737:chemistry; D008175:Lung Neoplasms / Q000737:chemistry; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D011485:Protein Binding; D025941:Protein Interaction Mapping; D011499:Protein Processing, Post-Translational; D051736:Proto-Oncogene Proteins c-mdm2 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D020798:Two-Hybrid System Techniques; D054875:Ubiquitination
D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; C434957:RYBP protein, human; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D005047:Etoposide; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2