Cloning of Senescent Cell-Derived Inhibitors of DNA Synthesis Using an Expression Screen

p21WAF1 induces permanent growth arrest and enhances differentiation, but does not alter apoptosis in PC12 cells

“…In the clonal lines described in this study, two showed no evidence of further proliferation, and in another, only rare`islands' of proliferating cells arose in the continued presence of IPTG. Overexpression of p21 has previously been shown to induce arrest (ElDeiry et al, 1993;Harper et al, 1993;Noda et al, 1994) mainly in G1, though most of these studies examined short term arrest via p21 (no more than 4 days) Katayose et al, 1995;Chen et al, 1996). Prolonged induction of p21 in other cell lines has resulted in various e ects, including apoptotic death (Sheikh et al, 1995), necrotic death (Givol et al, 1995), or decreased proliferation (not total inhibition) (Chen et al, 1995).…”

“…Additionally, induction may result from exogenous signals, such as inducers of differentiation, leading to the inhibition of proliferation (Sherr and Roberts, 1995;Harper and Elledge, 1996). p21 (known as WAF1, SDI1, MDA-6, CIP1 and CAP20) was the ®rst CDKI isolated, based on interactions with CDK2 (Gu et al, 1993;Harper et al, 1993) and PCNA (Xiong et al, 1992), as well as induction associated with p53 tumor-suppressor expression (El-Deiry et al, 1993), terminal di erentiation of human melanoma cells (Jiang and Fisher, 1993), and senescence of human diploid ®broblasts (Noda et al, 1994). p21 has not only been shown to inhibit the activity of a wide array of CDK-cyclin complexes (Xiong et al, 1993;Harper et al, 1995), but also inhibits DNA replication through its interaction with PCNA (Waga et al, 1994;Flores-Rozas et al, 1994).…”

Loss of p21Sdi1 expression in senescent cells after DNA damage accompanied with increase of miR-93 expression and reduced p53 interaction with p21Sdi1 gene promoter

“…The p21 waf1/cip1/sdi1 (p21), a cyclin E/Cdk2 inhibitor, is a direct transcriptional target of p53 and links the p53 and pRb pathways in human cells [7][8][9]. p21 is involved in the Ras G12V -induced senescence in different human cells; inhibition of p21 expression results in Ras G12V -resistant growth in BJ foreskin fibroblasts [10] and LF1 human lung fibroblasts [11].…”

Involvement of p21 in mitotic exit after paclitaxel treatment in MCF-7 breast adenocarcinoma cell line

“…p21 may inhibit cell cycle progression not only by inhibiting cdk activity but also by binding directly to the proliferating cell nuclear antigen (PCNA) (Waga et al, 1994). p21 is also induced by p53 independent pathways during cell senescence (Noda et al, 1994), cell di erentiation (Jiang et al, 1994;Steinman et al, 1994), as well as during the transition from quiescence to proliferation after addition of growth factors (Macleod et al, 1995). The expression of p21 is regulated during the cell cycle.…”