Staf50 is a novel p53 target gene conferring reduced clonogenic growth of leukemic U-937 cells

Abstract

The tumor suppressor gene p53 is a transcription factor that mediates both cell cycle arrest and apoptosis. Interestingly, p53 also induces differentiation of a number of tissues, including leukemic cells. However, although p53-mediated differentiation of leukemic U-937 cells depends on the transcriptional activity of p53, a p53 target gene mediating differentiation has hitherto not been identified. To screen for novel p53 target genes in leukemic cells, a cDNA microarray analysis was performed with U-937-4/ptsp53 cells, expressing a temperature-sensitive p53 mutant. We report that transcription of the Staf50 (stimulated transacting factor of 50 kDa) gene is upregulated in response to wild-type p53 in U-937-4, K562 and MCF-7 cells. Staf50 was directly activated by p53, as determined by the independence of de novo protein synthesis. Moreover, while the proximal promoter of Staf50 was found not to be p53 responsive, a functional enhancer-like p53-response element in intron 1 of the Staf50 gene was identified that was also transactivated by the p53-family member p73. Direct binding of p53 to the response element was shown by electrophoretic mobility shift analysis. Ectopic expression of Staf50 in U-937 cells resulted in reduced clonogenic growth. Moreover, levels of endogenous Staf50 mRNA correlated to all-trans retinoic acid-induced differentiation of promyelocytic NB-4 and HL60 cells, suggesting that Staf50 could be involved in proliferation and/or differentiation of leukemic cells.

TP53INP1 is a novel p73 target gene that induces cell cycle arrest and cell death by modulating p73 transcriptional activity

“…These effects are achieved through the activation of a plethora of specific target genes. Several reports show that p73 can bind p53-responsive elements and activate some p53 target genes (Stiewe and Pu¨tzer, 2001;Obad et al, 2004). These data strengthen the notion that these two proteins may cooperate in overlapping but distinct cell growth and apoptosis signalling pathways in response to stress.…”

Precision autophagy directed by receptor regulators – emerging examples within the TRIM family

“…In turn, TRIMs and p53 affect each other transcriptionally. TRIM3 increases the level of p53 (Cheung et al, 2010), and the expression of TRIM22 is increased by p53 (Obad et al, 2004), whereas that of TRIM9 is increased by mutated p53 (Okaichi et al, 2013). The relationship between TRIMs and p53 fit with the dual role of p53 in autophagy Tavernarakis et al, 2008).…”

Identification of the p53 family-responsive element in the promoter region of the tumor suppressor gene hypermethylated in cancer 1

“…Endogenous wild-type p53 activates transcription of HIC1 mRNA The human breast adenocarcinoma cell line MCF7 has been shown to activate endogenous wild-type p53 in response to UV-induced DNA damage, leading to increased expression of p53 target genes (Obad et al, 2004). To examine whether under this condition endogenous p53 is inducing HIC1 mRNA expression, we UV-irradiated MCF7 cells and assessed HIC1 mRNA changes by RQ-PCR.…”