%0 Journal Article
%T S100A13 promotes senescence-associated secretory phenotype and cellular senescence via modulation of non-classical secretion of IL-1¦Á
%A Chenzhong Xu
%A Guodong Li
%A Jun Chen
%A Tanjun Tong
%A Yao Liang
%A Yuanyuan Su
%A Zhaomeng Sun
%J Archive of "Aging (Albany NY)".
%D 2019
%R 10.18632/aging.101760
%X Senescent cells display the senescence-associated secretory phenotype (SASP) which plays important roles in cancer, aging, etc. Cell surface-bound IL-1¦Á is a crucial SASP factor and acts as an upstream regulator to induce NF-¦ÊB activity and subsequent SASP genes transcription. IL-1¦Á exports to cell surface via S100A13 protein-dependent non-classical secretory pathway. However, the status of this secretory pathway during cellular senescence and its role in cellular senescence remain unknown. Here, we show that S100A13 is up-regulated in various types of cellular senescence. S100A13 overexpression increases cell surface-associated IL-1¦Á level, NF-¦ÊB activity and subsequent multiple SASP genes induction, whereas S100A13 knockdown has an opposite role. We also exhibit that Cu2+ level is elevated during cellular senescence. Lowering Cu2+ level decreases cell surface-bound IL-1¦Á level, NF-¦ÊB activity and SASP production. Moreover, S100A13 overexpression promotes oncogene Ras-induced cell senescence (Ras OIS), Doxorubicin-induced cancer cell senescence (TIS) and replicative senescence, while impairment of non-classical secretory pathway of IL-1¦Á delays cellular senescence. In addition, intervention of S100A13 affects multiple SASP and cellular senescence mediators including p38, ¦Ã-H2AX, and mTORC1. Taken together, our findings unveil a critical role of the non-classical secretory pathway of IL-1¦Á in cellular senescence and SASP regulation
%K S100A13
%K non-classical protein secretory pathway
%K IL-1¦Á
%K SASP
%K Cu2+
%K cell senescence
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6366962/