Open AccessChemokine receptor CXCR 2 is transactivated by p53 and induces p38‐mediated cellular senescence in response to DNA damage
Author(s) -
Guo Haiyang,
Liu Zhaojian,
Xu Bing,
Hu Huili,
Wei Zhao,
Liu Qiao,
Zhang Xiyu,
Ding Xuebin,
Wang Yu,
Zhao Minnan,
Gong Yaoqin,
Shao Changshun
Publication year - 2013
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12138
Subject(s) - senescence , dna damage , biology , downregulation and upregulation , microbiology and biotechnology , chemokine receptor , chemokine , cancer research , receptor , gene , dna , genetics
Summary Mammalian cells may undergo permanent growth arrest/senescence when they incur excessive DNA damage. As a key player during DNA damage response ( DDR ), p53 transactivates an array of target genes that are involved in various cellular processes including the induction of cellular senescence. Chemokine receptor CXCR 2 was previously reported to mediate replicative and oncogene‐induced senescence in a DDR and p53‐dependent manner. Here, we report that CXCR 2 is upregulated in various types of cells in response to genotoxic or oxidative stress. Unexpectedly, we found that the upregulation of CXCR 2 depends on the function of p53. Like other p53 target genes such as p21, CXCR 2 is transactivated by p53. We identified a p53‐binding site in the CXCR 2 promoter that responds to changes in p53 functional status. Thus, CXCR 2 may act downstream of p53. While the senescence‐associated secretory phenotype (SASP) exhibits a kinetics that is distinct from that of CXCR 2 expression and does not require p53, it reinforces senescence. We further showed that the cellular senescence caused by CXCR 2 upregulation is mediated by p38 activation. Our results thus demonstrate CXCR 2 as a critical mediator of cellular senescence downstream of p53 in response to DNA damage.