Transcriptional repression mediated by the p53 tumour suppressor

Ho, Jason; Benchimol, Samuel

doi:10.1038/sj.cdd.4401191

Cited by 181 publications

(201 citation statements)

References 80 publications

Supporting

Mentioning

197

Contrasting

Order By: Relevance

“…16 Third, the co-binding of p53 and Slug to the same genomic region may interfere with p53 transcriptional activation by multiple mechanisms, such as interference with the proper assembly of the transcriptional machinery. 17 These models are consistent with the earlier kinetics of Slug induction as compared with Puma, allowing sufficient time for Slug accumulation. In fact, Slug appears to occupy the puma site even in unstressed hematopoietic progenitor cells and suppress its expression, supporting a role for Slug in the regulation of basal expression of puma.…”

Section: Slugging Puma Controls P53-induced Deathsupporting

confidence: 76%

Clues from worms: a Slug at Puma promotes the survival of blood progenitors

Haupt¹,

Alsheich-Bartok²,

Haupt³

2006

Cell Death Differ

View full text Add to dashboard Cite

Section: Slugging Puma Controls P53-induced Deathsupporting

confidence: 76%

Clues from worms: a Slug at Puma promotes the survival of blood progenitors

Haupt¹,

Alsheich-Bartok²,

Haupt³

2006

Cell Death Differ

View full text Add to dashboard Cite

“…The extranuclear p53 can directly activate Bax 35 or directly binds to Bcl-xL and Bcl-2 proteins to induce mitochondrial permeabilization and release cytochrome c, 36,37 which can promote caspase-3 activation. In addition to the direct transcriptional effect on caspases, their activators, and proapoptotic molecules of the Bcl-2 family, p53 can induce transcriptional repression of antiapoptotic genes 38 including Bcl-2 and surviving. Thus, direct upregulation of caspases and other proapoptotic molecules by p53 underscores the importance of p53 in cisplatin-induced AKI.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional activation of caspase-6 and -7 genes by cisplatin-induced p53 and its functional significance in cisplatin nephrotoxicity

et al. 2007

View full text Add to dashboard Cite

This study examined the role of cisplatin-induced p53 activation in regulation of caspases and cellular injury during cisplatin nephrotoxicity. The executioner caspase-6 and -7 but not caspase-3 were identified as transcriptional targets of p53 in cisplatin injury as revealed by chromatin immunoprecipitation, a reporter gene and electrophoretic mobility shift assays, and real-time PCR following overexpression and inhibition of p53. DNA binding by p53 involved the first introns of the human and mouse caspase-7 gene and the mouse caspase-6 gene. Studies in human kidney, breast, ovary, colon, and prostate tumor cell lines also validated these findings. Treatment of p53 (À/À) cells with cisplatin did not induce caspase-6 and -7 expression and subsequent activation. In caspase-3 (À/À) cells, inhibition of caspase-6 and -7 activations markedly prevented cisplatin-induced cell death.In an in vivo model of cisplatin nephrotoxicity inhibition of p53 activation by a p53 inhibitor suppressed transactivation of the caspase-6 and -7 genes and prevented renal failure. p53 (À/À) mice were resistant to cisplatin nephrotoxicity as assessed by renal function and histology. These studies provide first evidence for p53-dependent transcriptional control of the caspase-6 and -7 genes and its functional significance in cisplatin injury to renal cells and functional implication of cisplatin-induced p53 induction in vitro and in vivo in cisplatin nephrotoxicity.

show abstract

“…Transcription repression of downstream target genes by p53 is thought to occur via one of a few mechanisms (Ho and Benchimol, 2003). p53 may directly bind to p53 consensus to repress promoter activity or it may act through interference of the basal transcriptional machinery via the binding of p53 to the TATA-binding protein (Farmer et al, 1996) or the binding of other transcriptional factors.…”

Section: Fat10 Is Negatively Regulated By P53mentioning

confidence: 99%

“…p53, hailed as the 'guardian of the genome' (Lane, 1992), plays important roles in the regulation of cell cycle, response to DNA damage and apoptosis (Levine, 1997;Haupt et al, 2002;Vousden and Lu, 2002). p53 is a nuclear phosphoprotein that acts as a transcriptional regulator to modulate the expression of numerous downstream target genes both positively and negatively (el-Deiry, 1998;Ho and Benchimol, 2003). It can trans-activate cell-cycle/apoptotic genes, like MDM2, p21 WAF1/CIP1 and BAX, through the binding of a consensus sequence, 5 0 -PuPuPuC(A/T)(A/T)GPyPyPy-3 0 (two copies separated by 0-13 bp), in the target gene (el-Deiry, 1998;Vogelstein et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

p53 negatively regulates the expression of FAT10, a gene upregulated in various cancers

2006

View full text Add to dashboard Cite

FAT10 is a member of the ubiquitin-like modifier family of proteins and has been implicated to play important roles in antigen presentation, cytokine response, apoptosis and mitosis. We have recently demonstrated the upregulation of FAT10 gene expression in 90% of hepatocellular carcinoma patients. Here, we identified and characterized the promoter of the FAT10 gene to elucidate the mechanism of FAT10 gene expression. Notably, we found that the 5 0 untranslated region (5 0 UTR), from the transcription start site to 15 bases before the translational start site, displays significant promoter activity. Regions upstream of the 5 0 UTR (from þ 26 to À1997) do not confer any promoter activity. Curiously, FAT10 promoter activity and expression is significantly repressed in KB3-1 and HepG2 cells, which have wild-type p53, than in p53-negative Hep3B cells. The role of p53 in regulating FAT10 expression was evident by the significant downregulation (Po0.05) of FAT10 mRNA expression and promoter activity when wild-type p53 was transfected into p53-null Hep3B cells. Conversely, inhibiting p53 expression through siRNA against p53 significantly enhanced FAT10 expression and promoter activity. p53 was found to bind in vivo to the 5 0 half consensus sequence of p53-binding site located at the FAT10 promoter. Hence, we propose that FAT10 is a downstream target of p53 and dysregulation of FAT10 expression in p53-defective cells could contribute to carcinogenesis.

show abstract

Transcriptional repression mediated by the p53 tumour suppressor

Cited by 181 publications

References 80 publications

Clues from worms: a Slug at Puma promotes the survival of blood progenitors

Clues from worms: a Slug at Puma promotes the survival of blood progenitors

Transcriptional activation of caspase-6 and -7 genes by cisplatin-induced p53 and its functional significance in cisplatin nephrotoxicity

p53 negatively regulates the expression of FAT10, a gene upregulated in various cancers

Contact Info

Product

Resources

About