RGD Reference Report - Rapamycin induces pluripotent genes associated with avoidance of replicative senescence. - Rat Genome Database

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Rapamycin induces pluripotent genes associated with avoidance of replicative senescence.

Authors: Pospelova, TV  Bykova, TV  Zubova, SG  Katolikova, NV  Yartzeva, NM  Pospelov, VA 
Citation: Pospelova TV, etal., Cell Cycle. 2013 Dec 15;12(24):3841-51. doi: 10.4161/cc.27396. Epub 2013 Dec 2.
RGD ID: 9589808
Pubmed: PMID:24296616   (View Abstract at PubMed)
PMCID: PMC3905076   (View Article at PubMed Central)
DOI: DOI:10.4161/cc.27396   (Journal Full-text)

Primary rodent cells undergo replicative senescence, independent from telomere shortening. We have recently shown that treatment with rapamycin during passages 3-7 suppressed replicative senescence in rat embryonic fibroblasts (REFs), which otherwise occurred by 10-14 passages. Here, we further investigated rapamycin-primed cells for an extended number of passages. Rapamycin-primed cells continued to proliferate without accumulation of senescent markers. Importantly, these cells retained the ability to undergo serum starvation- and etoposide-induced cell cycle arrest. The p53/p21 pathway was functional. This indicates that rapamycin did not cause either transformation or loss of cell cycle checkpoints. We found that rapamycin activated transcription of pluripotent genes, oct-4, sox-2, nanog, as well as further upregulated telomerase (tert) gene. The rapamycin-derived cells have mostly non-rearranged, near-normal karyotype. Still, when cultivated for a higher number of passages, these cells acquired a chromosomal marker within the chromosome 3. We conclude that suppression mTORC1 activity may prevent replicative senescence without transformation of rodent cells.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
NanogRatcellular response to rapamycin  IEP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Nanog  (Nanog homeobox)


Additional Information