Aging Overview

External factors

External factors: CAPERα-TBX3 repressor complex
Aging type: Prevent
Aging characteristic:
Category: Other
Phenotype: Aging
Experimental category: HL
Tissue type: --
Cell name: HEK293,Primary HFF,MEF
PMID: 24876127
Experiment: Knockdown//SA-β-gal activity assay//Immunostaining//qRT-PCR//Western blot
Description: Knockdown of either protein resulted in a dramatic increase in senescence associated β-galatosidase activity.This effect is specific because it occurs with two different shRNAs and is rescued by overexpression of CAPERα and Tbx3. Expression of senescence mediators was increased and conversely, expression of cell growth and cell cycle promoting genes was similarly decreased by CAPERα and TBX3 KD .


Regulatory relationship

Target gene: LNCRNA UCA1
R-EF-Target gene: Downregulation
Official symbol(s): LNCRNA UCA1
Target gene experiment: qRT-PCR//CHIP-PCR
Target gene description: We found that shRNA KD of CAPERα or TBX3 in primary HFFS recapitulated the increase in UCA1 transcripts seen in HEK293 cells.After TBX3 KD, activating chromatin marks replaced repressive ones and markedly less CAPERα was bound. CAPERα KD also led to loss of repressive marks on UCA1/A3 , although TBX3 remained bound .

Regulatory pathway: p16-Rb
R-EF-Pathway: Downregulation
Official symbol(s): CDKN2A-RB1
Pathway experiment: Knockdown//SA-β-gal activity assay//qRT-PCR
Pathway description: Increased expression of CDKN2A-p16INK (henceforth referred to as p16INK) and decreased PCNA, E2F1 and 2, CDK2, CDK4, CDC2 transcripts indicate that CAPERα/TBX3 represses the p16/RB pathway in proliferating HFFs.In contrast, shRNA-mediated KD of either RB or p16 rescued these phenotypes in TBX3 and CAPERα KD cells .


Aging network

Annotation:

The green line represents Upregulation.

The purple line represents Downregulation.

The orange line represents Activation.

The yellow line represents Inhibition.

The gray line represents Unclear.



Pathway view