CD36 initiates the secretory phenotype during the establishment of cellular senescence.

Published

Journal Article

Cellular senescence is a unique cell fate characterized by stable proliferative arrest and the extensive production and secretion of various inflammatory proteins, a phenomenon known as the senescence-associated secretory phenotype (SASP). The molecular mechanisms responsible for generating a SASP in response to senescent stimuli remain largely obscure. Here, using unbiased gene expression profiling, we discover that the scavenger receptor CD36 is rapidly upregulated in multiple cell types in response to replicative, oncogenic, and chemical senescent stimuli. Moreover, ectopic CD36 expression in dividing mammalian cells is sufficient to initiate the production of a large subset of the known SASP components via activation of canonical Src-p38-NF-κB signaling, resulting in the onset of a full senescent state. The secretome is further shown to be ligand-dependent, as amyloid-beta (Aβ) is sufficient to drive CD36-dependent NF-κB and SASP activation. Finally, loss-of-function experiments revealed a strict requirement for CD36 in secretory molecule production during conventional senescence reprogramming. Taken together, these results uncover the Aβ-CD36-NF-κB signaling axis as an important regulator of the senescent cell fate via induction of the SASP.

Full Text

Duke Authors

Cited Authors

  • Chong, M; Yin, T; Chen, R; Xiang, H; Yuan, L; Ding, Y; Pan, CC; Tang, Z; Alexander, PB; Li, Q-J; Wang, X-F

Published Date

  • June 2018

Published In

Volume / Issue

  • 19 / 6

PubMed ID

  • 29777051

Pubmed Central ID

  • 29777051

Electronic International Standard Serial Number (EISSN)

  • 1469-3178

Digital Object Identifier (DOI)

  • 10.15252/embr.201745274

Language

  • eng

Conference Location

  • England