Apr 23, 2024 · Both p53–p21 and p16 directly regulate the SASP: p21 supports an early secretory phenotype that includes CXCL14 and IGFBP3, which puts stressed or senescent cells under immunosurveillance,...

We found that p21—in addition to its function in maintaining the cell-cycle arrest of SNCs—has a prominent role in establishing the SASP through retinoblastoma protein (Rb)–dependent transcription involving select SMAD and STAT transcription factors.

p21 regulates the SASP through Rb-dependent transcription. In our initial screen, we exposed primary mouse embryonic fibroblasts (MEFs) to three distinct senescence-inducing stressors: γ-irradiation (IR), extensive replication (REP), and oncogene-induced (OI) signaling by overexpression of human KRAS G12V .

The p21-induced secretome is characterized by the release of additional immunosurveillance factors, in particular Cxcl14, which are lacking in the p16INK4A-induced SASP. Consequently, the p21-induced secretome attracts macrophages.

Apr 24, 2024 · Cellular senescence is a state of terminal growth arrest associated with the upregulation of different cell cycle inhibitors, mainly p16 and p21, structural and metabolic alterations, chronic DNA damage responses, and a hypersecretory state known as the senescence-associated secretory phenotype (SASP).

Oct 7, 2021 · The p21-Cre mouse model allows us to suppress the SASP only in p21 high cells, so it is a cleaner system for examining the contribution of the SASP to age-related disorders.

Jan 1, 2023 · We show that p21 induces several core properties of cellular senescence in skeletal muscle, including an altered transcriptome, DNA damage, mitochondrial dysfunction, and the senescence-associated secretory phenotype (SASP).

Feb 15, 2018 · Here we demonstrated that various melanoma cell lines adopted senescence phenotype after CDDP treatment in contrast to the other types of tumour cells. CDDP treatment induced melanoma A375 cells...

Jul 9, 2017 · In this study, we have shown that both Akt and p21 are required to induce cellular senescence in response to p53 expression. In a p53‐induced senescence model, we found that Akt activation was essential for inducing a cellular senescence phenotype.

Dec 18, 2012 · Etoposide-treated cells exhibited a senescent phenotype characterized by senile morphology, positive staining for senescence-associated β-galactosidase, growth arrest and induction of p53 and p21 WAF1/CIP1. In SASP-RAP-transfected cells, exposure to etoposide increased secretion of SASP-RAP time-dependently.