10.6084/M9.FIGSHARE.13218148
Yinfeng Xu
Yinfeng
Xu
Yaosen Wu
Yaosen
Wu
Lei Wang
Lei
Wang
Chuying Qian
Chuying
Qian
Qian Wang
Qian
Wang
Wei Wan
Wei
Wan
Identification of curcumin as a novel natural inhibitor of rDNA transcription
<p>Ribosomal DNA (rDNA) transcription drives cell growth and cell proliferation via the product ribosomal RNA (rRNA), the essential component of ribosome. Given the fundamental role of rRNA in ribosome biogenesis, rDNA transcription has emerged as one of the effective targets for a number of human diseases including various types of cancers. In this study, we identify curcumin, an ancient drug, as a novel natural inhibitor of rDNA transcription. Curcumin treatment impairs the assembly of the RNA polymerase I preinitiation complex at rDNA promoters and represses rDNA promoter activity, which leads to the decrease of rRNA synthesis. In addition, curcumin treatment stimulates autophagosome formation and promotes autophagic degradation in cells. Mechanistically, curcumin inactivates the mechanistic target of rapamycin complex 1 (mTORC1), the upstream regulator of rDNA transcription and autophagy induction, by inhibiting mTOR lysosomal localization. Functionally, curcumin treatment inhibits protein synthesis, cell growth and cell proliferation. Taken together, these findings identify curcumin as an effective inhibitor of rDNA transcription and provide novel mechanisms for the anticancer properties of curcumin.</p> <p><b>Abbreviations:</b></p> <p>Atg: autophagy-related; GFP: green fluorescent protein; LAMP2: lysosomal associated membrane protein 2; LC3: microtubule-associated protein 1 light chain 3; MEF: mouse embryonic fibroblast; mTORC1: mechanistic target of rapamycin complex 1; rDNA: ribosomal DNA; rRNA: ribosomal RNA; TP53INP2: tumor protein p53 inducible nuclear protein 2.</p>
Biophysics
Biochemistry
Microbiology
Cell Biology
Genetics
Molecular Biology
Pharmacology
Biotechnology
Chemical Sciences not elsewhere classified
Cancer
Inorganic Chemistry
Hematology
Taylor & Francis
2020
2020-11-10
2023-06-27
Journal contribution
887296 Bytes
10.1080/15384101.2020.1843817
CC BY 4.0