J Biol Chem 2000,
PMID: 10749849
Zhang, W; Geiman, D E; Shields, J M; Dang, D T; Mahatan, C S; Kaestner, K H; Biggs, J R; Kraft, A S; Yang, V W
An important mechanism by which the tumor suppressor p53 maintains genomic stability is to induce cell cycle arrest through activation of the cyclin-dependent kinase inhibitor p21(WAF1/Cip1) gene. We show that the gene encoding the gut-enriched Krüppel-like factor (GKLF, KLF4) is concurrently induced with p21(WAF1/Cip1) during serum deprivation and DNA damage elicited by methyl methanesulfonate. The increases in expression of both Gklf and p21(WAF1/Cip1) due to DNA damage are dependent on p53. Moreover, during the first 30 min of methyl methanesulfonate treatment, the rise in Gklf mRNA level precedes that in p21(WAF1/Cip1), suggesting that GKLF may be involved in the induction of p21(WAF1/Cip1). Indeed, GKLF activates p21(WAF1/Cip1) through a specific Sp1-like cis-element in the p21(WAF1/Cip1) proximal promoter. The same element is also required by p53 to activate the p21(WAF1/Cip1) promoter, although p53 does not bind to it. Potential mechanisms by which p53 activates the p21(WAF1/Cip1) promoter include a physical interaction between p53 and GKLF and the transcriptional induction of Gklf by p53. Consequently, the two transactivators cause a synergistic induction of the p21(WAF1/Cip1) promoter activity. The physiological relevance of GKLF in mediating p53-dependent induction of p21(WAF1/Cip1) is demonstrated by the ability of antisense Gklf oligonucleotides to block the production of p21(WAF1/Cip1) in response to p53 activation. These findings suggest that GKLF is an essential mediator of p53 in the transcriptional induction of p21(WAF1/Cip1) and may be part of a novel pathway by which cellular responses to stress are modulated.
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Text Mining Data
p21WAF1/Cip1 → Kruppel-like factor: "
The gut enriched
Kruppel-like factor ( Kruppel-like factor 4 )
mediates the transactivating effect of p53 on the
p21WAF1/Cip1 promoter
"
p21WAF1/Cip1 — p53: "
The gut enriched Kruppel-like factor ( Kruppel-like factor 4 ) mediates the transactivating effect of p53 on the p21WAF1/Cip1 promoter
"
p21 → p53: "
The increases in expression of both Gklf and p21 ( WAF1/Cip1 ) due to DNA damage are dependent on p53
"
p21 → p53: "
The same element is also required by p53 to activate the p21 ( WAF1/Cip1 ) promoter, although p53 does not bind to it
"
p21 → p53: "
Potential mechanisms by which p53 activates the p21 ( WAF1/Cip1 ) promoter include a physical interaction between p53 and GKLF and the transcriptional induction of Gklf by p53
"
p21 ⊣ p53: "
The physiological relevance of GKLF in mediating p53 dependent induction of p21 ( WAF1/Cip1 ) is demonstrated by the ability of antisense Gklf oligonucleotides to block the production of p21 ( WAF1/Cip1 ) in response to p53 activation
"
Manually curated Databases
In total, 1 gene pairs are associated to this article in curated databases