Abstract
The nucleolus harbors the machinery necessary to produce new ribosomes which are critical for protein synthesis. Nucleolar size, shape, and density are highly dynamic and can be adjusted to accommodate ribosome biogenesis according to the needs for protein synthesis. In cancer, cells undergo continuous proliferation; therefore, nucleolar activity is elevated due to their high demand for protein synthesis. The transcription factor and universal oncogene MYC promotes nucleolar activity by enhancing the transcription of ribosomal DNA (rDNA) and ribosomal proteins. This review summarizes the importance of nucleolar activity in mammalian cells, MYC’s role in nucleolar regulation in cancer, and discusses how a better understanding (and the potential inhibition) of aberrant nucleolar activity in cancer cells could lead to novel therapeutics.
Highlights
Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
In cases of hyperproliferation, a higher rate of protein synthesis and ribosome biogenesis must be achieved to allow for cell growth, and the nucleolus increases in size and density to accommodate those needs [1,2]
The presence of nutrients and growth factors in the cellular environment leads to the The presence of nutrients and growth factors in the cellular environment leads to the activation pathwaysthat thatpromote promotecell cell growth, including production of activation of of signaling signaling pathways growth, including thethe production of new new ribosomes
Summary
The presence of nutrients and growth factors in the cellular environment leads to the The presence of nutrients and growth factors in the cellular environment leads to the activation pathwaysthat thatpromote promotecell cell growth, including production of activation of of signaling signaling pathways growth, including thethe production of new new ribosomes. Containing a larger number of of ribosomes amplifies mRNA translation and leads to an increase in cell growth. 3. The MYC Family of Transcription Factors Are Key Regulators of Cell Growth proliferation, and the reconstitution of MYC by ectopic expression rescues this phenotype originally discovered a viral oncogene (v-myc) that caused Turned to developing andirectly understanding ofthe the protein [58–61] MYC-NICK, a cytoplasmic proteolytic product of MYC that lacks proliferation, and the reconstitution of MYC by ectopic expression rescues this phenotype the DNA binding domain and is unable to regulate gene transcription, was (Figure 3A). The structure of the basic helix-loop-helix andand leucine zipper domains of the the heterodimer and (PDBe-KD), DNA (PDBe-KD), https://www.ebi.ac.uk/pdbe/pdbe-kb/proheterodimer and DNA https://www.ebi.ac.uk/pdbe/pdbe-kb/proteins/
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