Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.7.7.6 (
RNA polymerase
)
34,946
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Cells control their metabolism through modulating the anabolic and catabolic pathways.
TP53INP2
/DOR (
tumor protein p53 inducible nuclear protein 2
), participates in cell catabolism by serving as a promoter of autophagy. Here we uncover a novel function of
TP53INP2
in protein synthesis, a major biosynthetic and energy-consuming anabolic process.
TP53INP2
localizes to the nucleolus through its nucleolar localization signal (NoLS) located at the C-terminal domain. Chromatin immunoprecipitation (ChIP) assays detected an association of
TP53INP2
with the ribosomal DNA (rDNA), when exclusion of
TP53INP2
from the nucleolus repressed rDNA promoter activity and the production of ribosomal RNA (rRNA) and proteins. The removal of
TP53INP2
also impaired the association of the POLR1/
RNA polymerase I
preinitiation complex (PIC) with rDNA. Further,
TP53INP2
interacts directly with POLR1 PIC, and is required for the assembly of the complex. These data indicate that
TP53INP2
promotes ribosome biogenesis through facilitating rRNA synthesis at the nucleolus, suggesting a dual role of
TP53INP2
in cell metabolism, assisting anabolism on the nucleolus, and stimulating catabolism off the nucleolus.
...
PMID:TP53INP2/DOR, a mediator of cell autophagy, promotes rDNA transcription via facilitating the assembly of the POLR1/RNA polymerase I preinitiation complex at rDNA promoters. 2717 2
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.
Abbreviations:
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
.
...
PMID:Identification of curcumin as a novel natural inhibitor of rDNA transcription. 3317 Oct 62
