p21 produces a bioactive secretome that places stressed cells under immunosurveillance.
Science
; 374(6567): eabb3420, 2021 Oct 29.
Article
in En
| MEDLINE
| ID: mdl-34709885
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cellular Senescence
/
Cyclin-Dependent Kinase Inhibitor p21
/
Immunologic Surveillance
Limits:
Animals
/
Humans
Language:
En
Journal:
Science
Year:
2021
Document type:
Article
Affiliation country:
Estados Unidos