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2014 ; 5
(5
): 402-26
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Nucleolar stress with and without p53
#MMPMID25482194
James A
; Wang Y
; Raje H
; Rosby R
; DiMario P
Nucleus
2014[Sep]; 5
(5
): 402-26
PMID25482194
show ga
A veritable explosion of primary research papers within the past 10 years focuses
on nucleolar and ribosomal stress, and for good reason: with ribosome
biosynthesis consuming ~80% of a cell's energy, nearly all metabolic and
signaling pathways lead ultimately to or from the nucleolus. We begin by
describing p53 activation upon nucleolar stress resulting in cell cycle arrest or
apoptosis. The significance of this mechanism cannot be understated, as
oncologists are now inducing nucleolar stress strategically in cancer cells as a
potential anti-cancer therapy. We also summarize the human ribosomopathies,
syndromes in which ribosome biogenesis or function are impaired leading to birth
defects or bone narrow failures; the perplexing problem in the ribosomopathies is
why only certain cells are affected despite the fact that the causative mutation
is systemic. We then describe p53-independent nucleolar stress, first in yeast
which lacks p53, and then in other model metazoans that lack MDM2, the critical
E3 ubiquitin ligase that normally inactivates p53. Do these presumably ancient
p53-independent nucleolar stress pathways remain latent in human cells? If they
still exist, can we use them to target >50% of known human cancers that lack
functional p53?
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