Published online 25 July 2005. doi:10.1083/jcb1703iti3
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 170, Number 3, 335-335
Ribosome cycling
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Nucleolar WDR12 (orange) helps coordinate ribosome biogenesis and the cell cycle.
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Ribosome biogenesis consumes up to 80% of the energy of the cell. To prevent wastage of all of that energy, coordination with the cell cycle is vital. Both ribosome biogenesis and cell proliferation go awry when a the integrity of a three-protein complex (Nop7p-Erb1p-Ytm1p) in yeast is disrupted. Now on page 367, Hölzel et al. show that a homologous complex comprised of Pes1-Bop1-WDR12 exists in mammals and, like its yeast counterpart, relates cell cycle progression to ribosomal RNA processing.
Like Pes1 and Bop1, which have been characterized previously, Hölzel et al. find that WDR12 is up-regulated in response to c-myc expression and cell proliferation. Pes1, Bop1, and WDR12 copurified in immunoprecipitation experiments.
A link between ribosome biogenesis and the cell cycle may be provided by p53. This protein accumulates when the rRNA-encoding nucleolus is disrupted. Here, the researchers found that a WDR12 variant (lacking the most NH2-terminal of its seven WD repeats) stabilized p53, localized to the nucleolus, and inhibited rRNA processing, causing the accumulation of the 32S precursor. Cells expressing this mutant WDR12 failed to proliferate normally.
p53 stabilization by the WDR12 mutation was not dependent on the tumor suppressor p19ARF, which is a known to disrupt the ubiquitination of p53. The actual mechanism of p53 stabilization is unclear. The Pes1-Bop1-WDR12 complex might actively regulate p53 turnover, or p53 stabilization might be a secondary effect of mutations in Bop1 or WDR12. Such mutations disrupt ribosome assembly so they probably lead to an accumulation of free ribosomal proteins, such as L5, L11, and L23. These proteins bind an inhibitor of p53, and may thus allow p53 to delay the cell cycle. 
Rabiya S. Tuma
rabiya{at}nasw.org
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Mammalian WDR12 is a novel member of the Pes1–Bop1 complex and is required for ribosome biogenesis and cell proliferation
- Michael Hölzel, Michaela Rohrmoser, Martin Schlee, Thomas Grimm, Thomas Harasim, Anastassia Malamoussi, Anita Gruber-Eber, Elisabeth Kremmer, Wolfgang Hiddemann, Georg W. Bornkamm, and Dirk Eick
J. Cell Biol. 2005 170: 367-378.
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