Ribosomal protein S9 is a novel B23/NPM-binding protein required for normal cell proliferation.
B23 (NPM/nucleophosmin) is a multifunctional nucleolar protein and a member of the nucleoplasmin superfamily of acidic histone chaperones. B23 is essential for normal embryonic development and plays an important role in genomic stability, ribosome biogenesis, and anti-apoptotic signaling. Altered protein expression or genomic mutation of B23 is encountered in many different forms of cancer. Although described as multifunctional, a genuine molecular function of B23 is not fully understood. Here we show that B23 is associated with a protein complex consisting of ribosomal proteins and ribosome-associated RNA helicases. A novel, RNA-independent interaction between ribosomal protein S9 (RPS9) and B23 was further investigated. We found that S9 binding requires an intact B23 oligomerization domain. Depletion of S9 by small interfering RNA resulted in decreased protein synthesis and G(1) cell cycle arrest, in association with induction of p53 target genes. We determined that S9 is a short-lived protein in the absence of ribosome biogenesis, and proteasomal inhibition significantly increased S9 protein level. Overexpression of B23 facilitated nucleolar storage of S9, whereas knockdown of B23 led to diminished levels of nucleolar S9. Our results suggest that B23 selectively stores, and protects ribosomal protein S9 in nucleoli and therefore could facilitate ribosome biogenesis.
Lindström
Mikael S
MS
Department of Radiation Oncology, University of North Carolina School of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599-7512, USA.
Zhang
Yanping
Y
D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002466:Cell Nucleolus / Q000235:genetics / Q000378:metabolism*; D047108:Embryonic Development / Q000235:genetics; D016193:G1 Phase / Q000235:genetics; D042822:Genomic Instability / Q000235:genetics; D006801:Humans; D018832:Molecular Chaperones / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000090243:Nucleophosmin; D014176:Protein Biosynthesis / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D020365:RNA Helicases / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D012269:Ribosomal Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012270:Ribosomes / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; D018832:Molecular Chaperones; D046912:Multiprotein Complexes; C000716967:NPM1 protein, human; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D012269:Ribosomal Proteins; D016159:Tumor Suppressor Protein p53; D000090243:Nucleophosmin; D020365:RNA Helicases