Nucleolar Stress: hallmarks, sensing mechanism and diseases

Yang, Kai; Yang, Jie; Yi, Jing

Nucleolar Stress: hallmarks, sensing mechanism and diseases

Authors:

Kai Yang^1,2, Jie Yang¹ and Jing Yi¹

Affiliations:

¹ Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, 200025, China.

² Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases with Integrated Chinese-Western Medicine, Shanghai Institute of Traumatology and Orthopedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, China.

Keywords:

nucleolar stress, ribosome biogenesis, NPM1, translocation, p53, MDM2, ribosomal proteins.

Abbreviations:

Act.D – Actinomycin D,

AD – Alzheimer’s disease,

AML – acute myeloid leukemia,

ARF – alternative reading frame,

CBS – cystathionine-β-synthase,

DFC – dense FC,

FC – fibrillar center,

GC – granular component,

KO – knockout,

PD – Parkinson’s disease,

Pol I – RNA Polymerase I

rDNA – ribosomal DNA,

RP – ribosomal protein,

rRNA – ribosomal RNA,

TF – transcription factor.

Corresponding Author(s):

Jing Yi, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Department of Biochemistry and Molecular Cell Biology, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai, 200025, China yijing@shsmu.edu.cn

Conflict of interest statement:

There is no conflict of interest.

Please cite this article as:

Kai Yang, Jie Yang and Jing Yi (2018). Nucleolar Stress: hallmarks, sensing mechanism and diseases. Cell Stress 2(6): 125-140. doi: 10.15698/cst2018.06.139

© 2018 Yang et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.

Abstract:

The nucleolus is a prominent subnuclear compartment, where ribosome biosynthesis takes place. Recently, the nucleolus has gained attention for its novel role in the regulation of cellular stress. Nucleolar stress is emerging as a new concept, which is characterized by diverse cellular insult-induced abnormalities in nucleolar structure and function, ultimately leading to activation of p53 or other stress signaling pathways and alterations in cell behavior. Despite a number of comprehensive reviews on this concept, straightforward and clear-cut way criteria for a nucleolar stress state, regarding the factors that elicit this state, the morphological and functional alterations as well as the rationale for p53 activation are still missing. Based on literature of the past two decades, we herein summarize the evolution of the concept and provide hallmarks of nucleolar stress. Along with updated information and thorough discussion of existing confusions in the field, we pay particular attention to the current understanding of the sensing mechanisms, i.e., how stress is integrated by p53. In addition, we propose our own emphasis regarding the role of nucleolar protein NPM1 in the hallmarks of nucleolar stress and sensing mechanisms. Finally, the links of nucleolar stress to human diseases are briefly and selectively introduced.