MDM2 Mediates Nonproteolytic Polyubiquitylation of the DEAD-Box RNA Helicase DDX24

• Published in: Molecular and cellular biology Vol. 34; no. 17; pp. 3321 - 3340
• Main Authors: Yamauchi, Takayoshi, Nishiyama, Masaaki, Moroishi, Toshiro, Yumimoto, Kanae, Nakayama, Keiichi I.
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 01.09.2014; American Society for Microbiology
• Subjects: Amino Acid Sequence; Conserved Sequence; DEAD-box RNA Helicases - chemistry; DEAD-box RNA Helicases - genetics; DEAD-box RNA Helicases - metabolism; HCT116 Cells; Humans; Molecular Sequence Data; Multiprotein Complexes - chemistry; Multiprotein Complexes - metabolism; Nuclear Proteins - chemistry; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Proteasome Endopeptidase Complex - metabolism; Protein Interaction Domains and Motifs; Protein Stability; Proteolysis; Proto-Oncogene Proteins c-mdm2 - chemistry; Proto-Oncogene Proteins c-mdm2 - genetics; Proto-Oncogene Proteins c-mdm2 - metabolism; Ribonucleoproteins - chemistry; Ribonucleoproteins - genetics; Ribonucleoproteins - metabolism; RNA Precursors - metabolism; RNA Processing, Post-Transcriptional; Sequence Homology, Amino Acid; Tumor Suppressor Protein p53 - chemistry; Tumor Suppressor Protein p53 - metabolism; Ubiquitination
• ISSN: 1098-5549; 0270-7306; 1098-5549
• DOI: 10.1128/MCB.00320-14

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.