Gene expression of the POU factor Brn-3a is regulated by two different promoters

Fraß, Beate; Vaßen, Lothar; Möröy, Tarik

doi:10.1016/s0167-4781(02)00540-7

Cited by 9 publications

(7 citation statements)

References 18 publications

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“…Like many other TATA-less promoters (35,36), cat-1 has several Sp1 and AP2 sites. Another common feature of TATA-less promoters is the presence of promoter elements downstream of the transcription start site (37,38). In this study, we show that the AARE element downstream of the start site is required for regulation of promoter activity during stress caused by amino acid limitation.…”

Section: Discussionmentioning

confidence: 60%

Transcriptional Control of the Arginine/Lysine Transporter, Cat-1, by Physiological Stress

Fernandez¹,

Lopez²,

Wang³

et al. 2003

Journal of Biological Chemistry

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Cells respond to physiological stress by phosphorylating the ␣ subunit of the translation initiation factor eIF2. This adaptive response inhibits protein synthesis and up-regulates genes essential for cell survival. Cat-1, the transporter for the essential amino acids, arginine and lysine, is one of the up-regulated genes. We previously showed that stress increases cat-1 expression by coordinated stabilization of the mRNA and increased mRNA translation. This induction is triggered by amino acid depletion and the unfolded protein response (UPR), which is caused by unfolded proteins in the endoplasmic reticulum. We show here that cat-1 gene transcription is also increased by cellular stress. Our studies demonstrate that the cat-1 gene promoter/regulatory region is TATA-less and is located in a region that includes 94 bases of the first exon. Transcription from this promoter is stimulated 8-fold by cellular stress. An amino acid response element within the first exon is shown to be required for the response to amino acid depletion but not to the UPR. The stimulation of transcription by amino acid depletion requires activation of GCN2 kinase, which phosphorylates eIF2␣. This phosphorylation also induces translation of the cat-1 mRNA, demonstrating that stress-induced transcriptional and translational control of cat-1 are downstream targets of a signaling pathway initiating with eIF2␣ phosphorylation. Our studies show that the increase in cat-1 gene expression by cellular stress involves at least three types of coordinate regulation: regulation of transcription, regulation of mRNA stability, and regulation of mRNA translation.

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Section: Discussionmentioning

confidence: 60%

Transcriptional Control of the Arginine/Lysine Transporter, Cat-1, by Physiological Stress

Fernandez¹,

Lopez²,

Wang³

et al. 2003

Journal of Biological Chemistry

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“…Expression of Brn-3a has been demonstrated in Ewing's sarcoma samples (Collum et al, 1992) and recently in a Ewing's sarcoma cell line (Frass et al, 2002). Identification of the EWS C-terminus as the domain required for interaction with Brn-3 proteins suggested that EWS fusion proteins might not interact with Brn-3 proteins since they lack the C-terminal domain of EWS.…”

Section: Brn-3a But Not Brn-3b Interacts With Ews/ets Fusion Proteinsmentioning

confidence: 99%

“…Brn-3a can cooperate with Ras to transform primary rat fibroblasts (Theil et al, 1993), and roles for Brn-3 proteins in oncogenesis are also suggested by their aberrant expression in cervical cancer cells and breast cancer cells . Significantly, Brn-3a is expressed in cancer cells of neuronal lineage, in some neuroblastomas (Smith and Latchman, 1996) and in Ewing's sarcoma cells (Collum et al, 1992;Frass et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

The effects of Brn-3a on neuronal differentiation and apoptosis are differentially modulated by EWS and its oncogenic derivative EWS/Fli-1

Gascoyne¹,

Thomas

Latchman³

2004

Oncogene

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The Brn-3 family of POU (Pit-Oct-Unc) homeodomain transcription factors regulate differentiation of neuronal cell types. The transcriptional activator Brn-3a is expressed in Ewing's sarcomas, which also express characteristic chimaeric proteins as a consequence of fusion of the TET family gene EWS to one of several ETS genes. We have previously demonstrated a physical interaction between Brn-3a and EWS proteins, and show here that the C-terminal POU domain but not N-terminal activation domain of Brn-3a can interact in vitro with the RNA-binding domain of EWS. Likely due to POU domain homology, the related factor Brn-3b can also interact with EWS, but to a lesser extent than Brn-3a. Importantly, Brn-3a but not Brn-3b interacts in vitro with chimaeric EWS/Fli-1, EWS/ATF-1 and EWS/ERG proteins. Furthermore, overexpression of EWS/Fli-1 but not EWS or Fli-1 inhibits Brn-3a-associated growth arrest and neurite outgrowth in neuronal cells, and specifically inhibits Brn-3a-dependent activation of p21 and SNAP-25 transcription. In contrast, upregulation of Bcl-2 expression and inhibition of apoptosis by Brn-3a is antagonized more by EWS than by EWS/Fli-1. These data demonstrate that oncogenic rearrangement of EWS to produce EWS/Fli-1 may enhance the antiapoptotic effect of Brn3a and inhibit its ability to promote neuronal differentiation.

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“…Its murine counterpart is known as Brn3a (also known as Brn3.0 or POU4f1). Brn3a promoter is TATAless (Frass et al 2002), and the protein acts as an autoregulatory transcription factor by recognizing certain sites present in the enhancer of the gene. These sites are present in clusters in two diVerent regions, known as proximal region and distal region, respectively at 5.4 to 5.6 kb and 9 kb upstream of the transcription start site in Brn3a gene (Trieu et al 1999), which is highly conserved in humans.…”

Section: Introductionmentioning

confidence: 99%

Molecular analysis of oncogenicity of the transcription factor, BRN3A, in cervical cancer cells

Purkayastha

Roy

2011

J Cancer Res Clin Oncol

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Gene expression of the POU factor Brn-3a is regulated by two different promoters

Cited by 9 publications

References 18 publications

Transcriptional Control of the Arginine/Lysine Transporter, Cat-1, by Physiological Stress

Transcriptional Control of the Arginine/Lysine Transporter, Cat-1, by Physiological Stress

The effects of Brn-3a on neuronal differentiation and apoptosis are differentially modulated by EWS and its oncogenic derivative EWS/Fli-1

Molecular analysis of oncogenicity of the transcription factor, BRN3A, in cervical cancer cells

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