title: MDM2 mediates nonproteolytic polyubiquitylation of the DEAD-Box RNA helicase DDX24.
abstract: MDM2 mediates the ubiquitylation and thereby triggers the proteasomal degradation of the tumor suppressor protein p53. However, genetic evidence suggests that MDM2 contributes to multiple regulatory networks independently of p53 degradation. We have now identified the DEAD-box RNA helicase DDX24 as a nucleolar protein that interacts with MDM2. DDX24 was found to bind to the central region of MDM2, resulting in the polyubiquitylation of DDX24 both in vitro and in vivo. Unexpectedly, however, the polyubiquitylation of DDX24 did not elicit its proteasomal degradation but rather promoted its association with preribosomal ribonucleoprotein (pre-rRNP) processing complexes that are required for the early steps of pre-rRNA processing. Consistently with these findings, depletion of DDX24 in cells impaired pre-rRNA processing and resulted both in abrogation of MDM2 function and in consequent p53 stabilization. Our results thus suggest an unexpected role of MDM2 in the nonproteolytic ubiquitylation of DDX24, which may contribute to the regulation of pre-rRNA processing.
authors: Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Higashi-ku, Fukuoka, Fukuoka, and CREST, Japan Science and Technology Agency (JST), Kawaguchi, Saitama, Japan.
authors: Takayoshi
authors: T
authors: Yamauchi
authors: Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Higashi-ku, Fukuoka, Fukuoka, and CREST, Japan Science and Technology Agency (JST), Kawaguchi, Saitama, Japan.
authors: Masaaki
authors: M
authors: Nishiyama
authors: Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Higashi-ku, Fukuoka, Fukuoka, and CREST, Japan Science and Technology Agency (JST), Kawaguchi, Saitama, Japan.
authors: Toshiro
authors: T
authors: Moroishi
authors: Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Higashi-ku, Fukuoka, Fukuoka, and CREST, Japan Science and Technology Agency (JST), Kawaguchi, Saitama, Japan.
authors: Kanae
authors: K
authors: Yumimoto
authors: Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Higashi-ku, Fukuoka, Fukuoka, and CREST, Japan Science and Technology Agency (JST), Kawaguchi, Saitama, Japan nakayak1@bioreg.kyushu-u.ac.jp.
authors: Keiichi I
authors: KI
authors: Nakayama
mesh_terms: D000595:Amino Acid Sequence; D017124:Conserved Sequence; D053487:DEAD-box RNA Helicases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D045325:HCT116 Cells; D006801:Humans; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs; D055550:Protein Stability; D059748:Proteolysis; D051736:Proto-Oncogene Proteins c-mdm2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012322:RNA Precursors / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D012261:Ribonucleoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D046912:Multiprotein Complexes; C499553:NIP7 protein, human; D009687:Nuclear Proteins; D012322:RNA Precursors; D012261:Ribonucleoproteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D046988:Proteasome Endopeptidase Complex; C412870:DDX24 protein, human; D053487:DEAD-box RNA Helicases