LncRNA GUARDIN suppresses cellular senescence through a LRP130-PGC1α-FOXO4-p21-dependent signaling axis
Sun, X.; FrancisThorne, R.; Zhang, X. D.; He, M.; Feng, S.-S.; Lu, X.; Wu, M.
Show abstract
The long non-coding RNA GUARDIN functions to protect genome stability. Inhibiting GUARDIN expression can alter cell fate decisions towards senescence or apoptosis, but the underlying molecular signals are unknown. Here we show that GUARDIN is an essential component of a transcriptional repressor complex involving LRP130 and PGC1 which suppresses FOXO4 expression. GUARDIN acts as a scaffold to stabilize LRP130/PGC1 heterodimers and their occupancy at the FOXO4 promotor. Destabilizing this complex by silencing of GUARDIN, LRP130 or PGC1 leads to FOXO4-dependent upregulation of p21, thereby driving cells into senescence. We also found that GUARDIN expression was induced by rapamycin, a senolytic agent that suppresses cell senescence. FOS-Like Antigen 2 (FOSL2) acts as a transcriptional repressor of GUARDIN with increased levels in the presence of rapamycin resulting from downregulation of FOSL2. Together, these results demonstrate that GUARDIN inhibits p21-dependent senescence through a LRP130-PGC1-FOXO4 signaling axis and moreover, GUARDIN contributes to the anti-senolytic activities of rapamycin.
Matching journals
The top 10 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- A role for fibroblast-derived SASP factors in the activation of pyroptotic cell death in mammary epithelial cells 95%
- Up-regulation of cholesterol synthesis by lysosomal defects requires a functional mitochondrial respiratory chain 95%
- Fragility of ER homeostatic regulation underlies haploid instability in human somatic cells 95%
Similar papers in this journal
- NRF1 and NRF3 complementarily maintain a basal proteasome activity in cancer cells through CPEB3-mediated translational repression 94%
- The Conserved CNOT1 Interaction Motif of Tristetraprolin Regulates ARE-mRNA Decay Independently of the p38 MAPK-MK2 Kinase Pathway 94%
- A non-canonical Hippo pathway represses the expression of deltaNp63 93%
Similar papers in this journal
- Cystathionine-β-synthase is essential for AKT-induced senescence and suppresses the development of gastric cancers with PI3K/AKT activation 95%
- Differential translation of mRNA isoforms underlies oncogenic activation of cell cycle kinase Aurora A 95%
- Isoform-specific Disruption of the TP73 Gene Reveals a Critical Role for TAp73gamma in Tumorigenesis via Leptin 95%
Similar papers in this journal
- ELP-dependent expression of MCL1 promotes resistance to EGFR inhibition in triple-negative breast cancer cells 94%
- Reporter-based screening identifies RAS-RAF stabilizing mutations as drivers of resistance to broad-spectrum RAS inhibition in colorectal cancer 94%
- Control of ribosomal protein synthesis by Microprocessor complex 93%
Similar papers in this journal
- Hypoxia increases the methylated histones to prevent histone clipping and redistribution of heterochromatin during Raf-induced senescence 96%
- Induction of senescence upon loss of the Ash2l core subunit of H3K4 methyltransferase complexes 95%
- Transcription factor RFX7 governs a tumor suppressor network in response to p53 and stress 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.