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P21 produces a bioactive secretome that places stressed cells under immunosurveillance.

ABSTRACT: Immune cells identify and destroy damaged cells to prevent them from causing cancer or other pathologies by mechanisms that remain poorly understood. Here, we report that the cell-cycle inhibitor p21 places cells under immunosurveillance to establish a biological timer mechanism that controls cell fate. p21 activates retinoblastoma protein (Rb)–dependent transcription at select gene promoters to generate a complex bioactive secretome, termed p21-activated secretory phenotype (PASP). The PASP includes the chemokine CXCL14, which promptly attracts macrophages. These macrophages disengage if cells normalize p21 within 4 days, but if p21 induction persists, they polarize toward an M1 phenotype and lymphocytes mount a cytotoxic T cell response to eliminate target cells, including preneoplastic cells. Thus, p21 concurrently induces proliferative arrest and immunosurveillance of cells under duress.

SUBMITTER: Sturmlechner I

PROVIDER: S-EPMC8985214 | biostudies-literature |

REPOSITORIES: biostudies-literature

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p21 produces a bioactive secretome that places stressed cells under immunosurveillance

Project description:This SuperSeries is composed of the SubSeries listed below.

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