
암유발 유전자 유도 노화 과정에서 TPR은 세포질 크로마틴 단편 형성과 이를 통한 NF-κB 신호 활성화에 필수적이다.


coremsg

During oncogene-induced senescence there are striking changes in the structure of the nucleus and the organisation of heterochromatin. This is accompanied by activation of a pro-inflammatory gene expression programme – the senescence associated secretory phenotype (SASP) – driven by transcription factors such as NF-κB. Here we show that TPR, a protein of the nuclear pore complex basket, is required for the very early activation of NF-κB signalling during the stress-response phase of oncogene-induced senescence. This is prior to activation of the SASP and occurs without affecting NF-κB nuclear import. We show that TPR is required for the activation of TBK1 signalling at these early stages of senescence and we link this to the formation of heterochromatin-enriched cytoplasmic chromatin fragments thought to bleb off from the nuclear periphery. These cytoplasmic chromatin fragments appear to lack nuclear pore components. Our data suggest that TPR at the nuclear pore is involved in the loss of structural integrity of the nuclear periphery during senescence. We propose that this acts as a trigger for activation of cytoplasmic nucleic acid sensing, NF-κB signalling, and activation of the SASP, during senescence.

### Competing Interest Statement

The authors have declared no competing interest.

TPR is required for cytoplasmic chromatin fragment formation during senescence

암유발-유전자-유도-노화-과정에서-세포질-크로마틴-단편-형성에-tpr이-필요하다


암유발 유전자 유도 노화 과정에서 세포질 크로마틴 단편 형성에 TPR이 필요하다
