Nukleolus tuottaa ribosomeja ja on "Organelle of Chief"

https://www.ncbi.nlm.nih.gov/pubmed/27528756

Biochem Soc Trans. 2016 Aug 15;44(4):1086-90. doi: 10.1042/BST20160106.

The importance of ribosome production, and the 5S RNP-MDM2 pathway, in health and disease.

Pelava A¹, Schneider C¹, Watkins NJ².

Author information

Abstract

Ribosomes are abundant, large RNA-protein complexes that are the source of all protein synthesis in the cell. The production of ribosomes is an extremely energetically expensive cellular process that has long been linked to human health and disease. More recently, it has been shown that ribosome biogenesis is intimately linked to multiple cellular signalling pathways and that defects in ribosome production can lead to a wide variety of human diseases. Furthermore, changes in ribosome production in response to nutrient levels in the diet lead to metabolic re-programming of the liver. Reduced or abnormal ribosome production in response to cellular stress or mutations in genes encoding factors critical for ribosome biogenesis causes the activation of the tumour suppressor p53, which leads to re-programming of cellular transcription. The ribosomal assembly intermediate 5S RNP (ribonucleoprotein particle), containing RPL5, RPL11 and the 5S rRNA, accumulates when ribosome biogenesis is blocked. The excess 5S RNP binds to murine double minute 2 (MDM2), the main p53-suppressor in the cell, inhibiting its function and leading to p53 activation. Here, we discuss the involvement of ribosome biogenesis in the homoeostasis of p53 in the cell and in human health and disease.

© 2016 The Author(s).

KEYWORDS:

5S RNP; MDM2; nucleolus; p53; ribosomal protein; ribosome

PMID:

27528756

PMCID:

PMC4984446

DOI:

10.1042/BST20160106

[Indexed for MEDLINE]

Free PMC Article
 Ribosome biogenesis and p53 signalling

(A) Schematic representation of ribosome biogenesis and the link between the 5S RNP and MDM2. Three of the rRNAs (18S, 5.8S and 28S) are transcribed by RNA polymerase I (Pol I) in the nucleolus, whereas the 5S rRNA is transcribed by RNA polymerase III (Pol III) in the nucleoplasm. The mature (18S, 5.8S, 28S and 5S) rRNAs and the precursor rRNAs (47S, 21S, 18SE, 32S and 7S) are indicated. The LSU ribosome biogenesis factors PAK1IP1 and PICT1 are shown. (B) Illustration of the 5S RNP interaction with MDM2 and the regulation of p53 signalling in both unstressed and stressed cells; Ub: ubiquitin.