SCAMP4 enhances the senescent cell secretome
- Kyoung Mi Kim1,3,
- Ji Heon Noh1,3,
- Monica Bodogai2,
- Jennifer L. Martindale1,
- Poonam R. Pandey1,
- Xiaoling Yang1,
- Arya Biragyn2,
- Kotb Abdelmohsen1 and
- Myriam Gorospe1
- 1Laboratory of Genetics and Genomics, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, Maryland 21224, USA;
- 2Laboratory of Molecular Biology and Immunology, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, Maryland 21224, USA
- Corresponding author: kyoungmi.kim{at}nih.gov
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↵3 These authors contributed equally to this work.
Abstract
The senescence-associated secretory phenotype (SASP) is a major trait of senescent cells, but the molecular regulators of SASP factor secretion are poorly understood. Mass spectrometry analysis revealed that secretory carrier membrane protein 4 (SCAMP4) levels were strikingly elevated on the surface of senescent cells compared with proliferating cells. Interestingly, silencing SCAMP4 in senescent fibroblasts reduced the secretion of SASP factors, including interleukin 6 (IL6), IL8, growth differentiation factor 15 (GDF-15), C-X-C motif chemokine ligand 1 (CXCL1), and IL7, while, conversely, SCAMP4 overexpression in proliferating fibroblasts increased SASP factor secretion. Our results indicate that SCAMP4 accumulates on the surface of senescent cells, promotes SASP factor secretion, and critically enhances the SASP phenotype.
Keywords
- human diploid fibroblasts
- SCAMP4
- senescence-associated secretory phenotype (SASP)
- cellular senescence
Footnotes
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Supplemental material is available for this article.
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Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.313270.118.
- Received February 16, 2018.
- Accepted May 22, 2018.
This is a work of the US Government.
