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Hiding proteins in the nucleolus

The Rockefeller University Press
Publication Date
DOI: 10.1083/jcb1705iti1
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1705iti In This Issue JCB • VOLUME 170 • NUMBER 5 • 2005696 Immortal DNA arpowicz et al. (page 721) report evidence for asymmetric segregation of the oldest DNA during neural stem cell proliferation. According to the immortal strand hypothesis, which was first proposed in the mid-1970s, stem cells actively retain the oldest DNA during asymmetric cell divisions. That DNA should, statistically speaking, contain fewer replication- induced errors than DNA resulting from more rounds of replication. While tanta- lizing for its logic, the hypothesis has been controversial, and numerous studies have failed to find evidence for it. Working with mouse neural stem cells, the authors labeled cells with BrdU and then looked at how the DNA segre- gated. When populations of cells were labeled, dispersed into single cells, and allowed to proliferate, they gave rise to neurospheres that frequently contained a few BrdU-labeled cells. The retention of the label after numerous divisions K Hiding proteins in the nucleolus ells regulate metabolic pathways by rigidly locking enzymes in the nucleolus, report Mekhail et al. on page 733. Two ubiquitin ligase enzymes bind in the nucleolus in response to signals that block their activity. Ubiquitin tagging alters protein fates, often marking substrates for degradation. Regulation of the process occurs at the level of the ubiquitin ligases, called E3s, which facilitate the transfer of ubiquitin from a conjugating enzyme to the target protein. Several E3 proteins aggregate in the nucleolus in response to inhibitory signals. The new results show that two different E3 enzymes, MDM2 and von Hippel-Lindau tumor suppressor (VHL), become immobilized in the structure and probably bind nucleolar scaffold proteins. In the presence of oxygen, VHL tags the hypoxia-inducible factor (HIF � ), causing its degradation. The authors identified a domain within VHL that detects increased acidity, such as occurs during hypoxia, and

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