Abstract
The nucleolus reacts to several forms of cellular stress, which disturb the normal nucleolar functions in ribosomal DNA (rDNA) transcription and ribosome assembly. These include agents that inhibit transcription by RNA polymerase I -complex, e.g. DNA damage or cytotoxic drugs. These cause so called “ribosomal stress” or “nucleolar stress” involving nucleolar disruption and induction of a stress response with tumor suppressor p53 and its negative regulator MDM2 as the key players. On the other hand, proteotoxic stress induced by e.g. hampered protein degradation due to proteasome inhibition or increased protein synthesis due to a viral infection, can cause formation of insoluble protein and RNA aggregates to nucleoli. These nucleolar aggresomes may reflect the connections of nucleoli in nuclear export of proteins and RNA. In addition, the nucleolus is central in the regulation of certain tumor suppressor and oncogene activities. The importance of these cellular processes and nucleolar stress responses are underscored in major diseases like cancer, ribosomopathies, and even inclusion diseases. In this chapter, we introduce the nucleolus as a stress-responsive organelle, and discuss the connections with human disease.
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Abbreviations
- Act D:
-
Actinomycin D
- DBA:
-
Diamond Blackfan anemia
- DFC:
-
Dense fibrillar component
- FC:
-
Fibrillar center
- GC:
-
Granular component
- HD:
-
Huntington’s disease
- Mdm2:
-
Mouse double minute 2
- OPMD:
-
Oculopharyngeal muscular dystrophy
- poly(A) RNA:
-
Polyadenylated RNA
- polyQ:
-
Polyglutamine
- rDNA:
-
Ribosomal DNA
- RNA pol:
-
RNA polymerase
- rRNA:
-
Ribosomal RNA
- SCA:
-
Spinocerebellar ataxia
- UPS:
-
Ubiquitin proteasome system
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Acknowledgements
The original work of LL related to this subject was supported by the Finnish Academy (grant no. 108828). Prof. Tapio Visakorpi for his kind support to LL. Research on the nucleolus and ribosomal proteins in the ML project group is supported by the Swedish Research Council, project number K2012-99X-2969-01-3, and the Karolinska Institutet.
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Lindström, M.S., Latonen, L. (2013). The Nucleolus as a Stress Response Organelle. In: O'Day, D., Catalano, A. (eds) Proteins of the Nucleolus. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5818-6_11
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