The 5S RNP couples p53 homeostasis to ribosome biogenesis and nucleolar stress

Katherine E Sloan1, Markus T Bohnsack, Nicholas J Watkins

  • 1ICaMB, 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.

Cell Reports
|October 15, 2013
PubMed

Insights

The 5S ribonucleoprotein particle (RNP) regulates p53 activation, linking cell proliferation to ribosome production. This ribosomal subcomplex, including 5S rRNA, RPL5, and RPL11, is crucial for tumor suppressor activity.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Oncology

Background:

  • Proto-oncogenes and tumor suppressors control ribosome production.
  • Ribosome biogenesis is energy-intensive, and defects trigger p53 activation.
  • Ribosomal proteins RPL5 and RPL11 repress MDM2 homolog, activating p53.

Purpose of the Study:

  • Investigate the role of the 5S ribonucleoprotein particle (RNP) in p53 regulation.
  • Determine the significance of 5S rRNA within the 5S RNP complex.
  • Elucidate the connection between 5S RNP, p14(ARF), and p53 activation.

Main Methods:

  • Analysis of ribosomal subcomplexes.
  • Investigation of protein-RNA interactions.
  • Study of p53 activation pathways.

Main Results:

  • RPL5 and RPL11 regulate p53 from within the 5S RNP.
  • 5S rRNA is essential for p53 regulation by the 5S RNP.
  • The 5S RNP is critical for p14(ARF)-mediated p53 activation.
  • PICT1 influences 5S RNP abundance and subsequent p53 levels.

Conclusions:

  • The 5S RNP acts as a key regulator of p53.
  • This complex links ribosome production with cell proliferation control.
  • The 5S RNP is a critical signaling hub in cancer-related pathways.

Related Concept Videos

The Nucleolus02:55

The Nucleolus

The nucleolus is the most prominent substructure of the nucleus. When it was first discovered, it was considered to be an isolated organelle that forms fibrils and granules. In 1931, the relationship between the nucleolus and chromosomes was first described by Heitz. He observed that the appearance and size of nucleolus varies depending on the stage of the cell cycle. He also noticed constricted regions on different chromosomes clustered together at definite cell cycle stages. These regions,...
8.6K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.0K
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
32.1K
RNA Stability01:53

RNA Stability

Intact DNA strands can be found in fossils, while scientists sometimes struggle to keep RNA intact under laboratory conditions. The structural variations between RNA and DNA underlie the differences in their stability and longevity. Because DNA is double-stranded, it is inherently more stable. The single-stranded structure of RNA is less stable but also more flexible and can form weak internal bonds. Additionally, most RNAs in the cell are relatively short, while DNA can be up to 250 million...
31.7K
RNA Stability01:53

RNA Stability

11.0K
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
2.4K