The study explores the p53-dependent and independent expression of p21 during cell growth, differentiation, and DNA damage. It shows that p21 expression is regulated by p53 in response to DNA-damaging agents, but can also occur independently in various tissues during development and in adult mice. p21 is expressed in the absence of p53 function in many tissues, but p53 is required for p21 induction following γ irradiation. p21 is also expressed during differentiation of p53-deficient murine erythroleukemia (MEL) cells, suggesting a role in growth arrest preceding terminal differentiation. p21 expression is regulated by serum stimulation and is up-regulated in mouse fibroblasts, with differences in kinetics and levels between wild-type and p53-deficient cells. p21 expression is also regulated post-transcriptionally, as seen in the increased protein levels following serum restimulation. The p21 promoter contains two critical p53-binding sites, and serum responsiveness of the promoter overlaps with a functional p53 site. p21 is involved in growth arrest and is regulated by p53 in response to DNA damage. However, p21 can also be regulated independently of p53 in several situations, including during normal tissue development, following serum stimulation, and during cellular differentiation. The study highlights the complex regulation of p21 and its role in cell cycle control and tumor suppression.The study explores the p53-dependent and independent expression of p21 during cell growth, differentiation, and DNA damage. It shows that p21 expression is regulated by p53 in response to DNA-damaging agents, but can also occur independently in various tissues during development and in adult mice. p21 is expressed in the absence of p53 function in many tissues, but p53 is required for p21 induction following γ irradiation. p21 is also expressed during differentiation of p53-deficient murine erythroleukemia (MEL) cells, suggesting a role in growth arrest preceding terminal differentiation. p21 expression is regulated by serum stimulation and is up-regulated in mouse fibroblasts, with differences in kinetics and levels between wild-type and p53-deficient cells. p21 expression is also regulated post-transcriptionally, as seen in the increased protein levels following serum restimulation. The p21 promoter contains two critical p53-binding sites, and serum responsiveness of the promoter overlaps with a functional p53 site. p21 is involved in growth arrest and is regulated by p53 in response to DNA damage. However, p21 can also be regulated independently of p53 in several situations, including during normal tissue development, following serum stimulation, and during cellular differentiation. The study highlights the complex regulation of p21 and its role in cell cycle control and tumor suppression.