title: The 5S RNP couples p53 homeostasis to ribosome biogenesis and nucleolar stress.
abstract: Several proto-oncogenes and tumor suppressors regulate the production of ribosomes. Ribosome biogenesis is a major consumer of cellular energy, and defects result in p53 activation via repression of mouse double minute 2 (MDM2) homolog by the ribosomal proteins RPL5 and RPL11. Here, we report that RPL5 and RPL11 regulate p53 from the context of a ribosomal subcomplex, the 5S ribonucleoprotein particle (RNP). We provide evidence that the third component of this complex, the 5S rRNA, is critical for p53 regulation. In addition, we show that the 5S RNP is essential for the activation of p53 by p14(ARF), a protein that is activated by oncogene overexpression. Our data show that the abundance of the 5S RNP, and therefore p53 levels, is determined by factors regulating 5S complex formation and ribosome integration, including the tumor suppressor PICT1. The 5S RNP therefore emerges as the critical coordinator of signaling pathways that couple cell proliferation with ribosome production.
authors.affiliation: ICaMB, Newcastle University, Newcastle upon Tyne NE2 4HH, UK; Centre for Biochemistry and Molecular Cell Biology, Institute for Molecular Biology, Medical Faculty, Georg-August University, 37073 Goettingen, Germany.
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Sloan
authors.forename: Markus T
authors.initials: MT
authors.lastname: Bohnsack
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Watkins
mesh_terms: D000818:Animals; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D002466:Cell Nucleolus / Q000378:metabolism*; D057809:HEK293 Cells; D006706:Homeostasis; D006801:Humans; D051379:Mice; D012341:RNA, Ribosomal, 5S / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D012341:RNA, Ribosomal, 5S; D016159:Tumor Suppressor Protein p53