1. Academic Validation
  2. NF-κB/IKK activation by small extracellular vesicles within the SASP

NF-κB/IKK activation by small extracellular vesicles within the SASP

  • Aging Cell. 2021 Jul;20(7):e13426. doi: 10.1111/acel.13426.
Juan Antonio Fafián-Labora 1 Ana O'Loghlen 1
Affiliations

Affiliation

  • 1 Epigenetics & Cellular Senescence Group, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Abstract

Cellular senescence plays an important role in different biological and pathological conditions. Senescent cells communicate with their microenvironment through a plethora of soluble factors, metalloproteases and extracellular vesicles (EV). Although much is known about the role that soluble factors play in senescence, the downstream signalling pathways activated by EV in senescence is unknown. To address this, we performed a small molecule inhibitor screen and have identified the IκB kinases IKKε, IKKα and IKKβ as essential for senescence mediated by EV (evSASP). By using pharmacological inhibitors of IKKε, IKKα and IKKβ, in addition to CRISPR/Cas9 targeting their respective genes, we find these pathways are important in mediating senescence. In addition, we find that senescence activation is dependent on canonical NF-κB transcription factors where siRNA targeting p65 prevent senescence. Importantly, these IKK pathways are also relevant to ageing as knockout of IKKA, IKKB and IKKE avoid the activation of senescence. Altogether, these findings open a new potential line of investigation in the field of senescence by targeting the negative effects of the evSASP independent of particular EV contents.

Keywords

IκB kinase (IKK); NF-κB; SASP; ageing; extracellular vesicles (EV); senescence.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-15473
    99.76%, IKKβ 抑制剂
    IKK