Journal
NUCLEUS
Volume 5, Issue 5, Pages 402-426Publisher
TAYLOR & FRANCIS INC
DOI: 10.4161/nucl.32235
Keywords
nucleolar stress; ribosomal proteins; cell cycle; p53; ribosomopathies
Categories
Funding
- National Science Foundation [MCB-0919709]
- Div Of Molecular and Cellular Bioscience
- Direct For Biological Sciences [0919709] Funding Source: National Science Foundation
Ask authors/readers for more resources
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 similar to 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?
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available