Regulation of the Pur-alpha promoter by E2F-1

Darbinian, Nune; White, Martyn K.; Khalili, Kamel

doi:10.1002/jcb.20872

Cited by 17 publications

(15 citation statements)

References 35 publications

(64 reference statements)

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“…own expression, and that it can be transactivated by E2F-1 (44). Our data suggest that both a reduced level of Pura and its exclusion from the nucleus can account for the loss of Pura from the AR 5 ¶-UTR in HR-PCs.…”

Section: Discussionmentioning

confidence: 67%

Androgen Receptor Overexpression in Prostate Cancer Linked to Purα Loss from a Novel Repressor Complex

et al. 2008

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Increased androgen receptor (AR) expression and activity are pivotal for androgen-independent (AI) prostate cancer (PC) progression and resistance to androgen-deprivation therapy. We show that a novel transcriptional repressor complex that binds a specific sequence (repressor element) in the AR gene 5 ¶-untranslated region contains PurA and hnRNP-K. PurA expression, its nuclear localization, and its AR promoter association, as determined by chromatin immunoprecipitation analysis, were found to be significantly diminished in AILNCaP cells and in hormone-refractory human PCs. Transfection of AI cells with a plasmid that restored PurA expression reduced AR at the transcription and protein levels. PurA knockdown in androgen-dependent cells yielded higher AR and reduced p21, a gene previously shown to be under negative control of AR. These changes were linked to increased proliferation in androgen-depleted conditions. Treatment of AI cells with histone deacetylase and DNA methylation inhibitors restored PurA protein and binding to the AR repressor element. This correlated with decreased AR mRNA and protein levels and inhibition of cell growth. PurA is therefore a key repressor of AR transcription and its loss from the transcriptional repressor complex is a determinant of AR overexpression and AI progression of PC. The success in restoring PurA and the repressor complex function by pharmacologic intervention opens a promising new therapeutic approach for advanced PC. [Cancer Res 2008;68(8):2678-88]

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Section: Discussionmentioning

confidence: 67%

Androgen Receptor Overexpression in Prostate Cancer Linked to Purα Loss from a Novel Repressor Complex

et al. 2008

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“…According to our results, NRSF would repress the expression of ST6GAL2, suggesting that the expression in SH-SY5Y cells could be disinhibited for precise neuronal-related function(s). Olf1, Sox5 and Purα are transcription factors that have been shown to be involved in neurogenesis and general neuronal functions [19,[47][48][49][50] and would argue for a specific neuronal expression of ST6GAL2. SP1 is generally an activator factor that binds GC-rich sequences and four putative SP1 binding sites lie within the two identified ST6GAL2 promoter sequences.…”

Section: Promoter Regions and Transcription Factorsmentioning

confidence: 99%

Transcriptional regulation of the human ST6GAL2 gene in cerebral cortex and neuronal cells

et al. 2009

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The second human beta-galactoside alpha-2,6-sialyltransferase (hST6Gal II) differs from hST6Gal I, the first member of ST6Gal family, in substrate specificity and tissue expression pattern. While ST6GAL1 gene is expressed in almost all human tissues, ST6GAL2 shows a restricted tissue-specific pattern of expression, mostly expressed in embryonic and adult brain. In order to understand the mechanisms involved in the transcriptional regulation of ST6GAL2, we first characterized the transcription start sites (TSS) in SH-SY5Y neuroblastoma cells. 5' RACE experiments revealed multiple TSS located on three first alternative 5' exons, termed EX, EY and EZ, which are unusually close on the genomic sequence and are all located more than 42 kbp upstream of the first common coding exon. Using Taqman duplex Q-PCR, we showed that the ST6GAL2 transcripts initiated by EX or EY are mainly expressed in both brain-related cell lines and human cerebral cortex, testifying for the use of a similar transcriptional regulation in vivo. Furthermore, we also showed for the first time hST6Gal II protein expression in the different lobes of the human cortex. Luciferase reporter assays allowed us to define two sequences upstream EX and EY with a high and moderate promoter activity, respectively. Bioinformatics analysis and site-directed mutagenesis showed that NF-kappaB and NRSF are likely to act as transcriptional repressors, whereas neuronal-related development factors Sox5, Puralpha and Olf1, are likely to act as transcriptional activators of ST6GAL2. This suggests that ST6GAL2 transcription could be potentially activated for specific neuronal functions.

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“…[9][10][11] Interestingly, Purα autoregulates its transcription, and exerts negative feedback through E2F-1. 12,13 In addition to mediating transcriptional activation, Purα is also an important replication factor that has the ability to regulate cell proliferation. The intracellular level of Purα varies throughout the cell cycle, declining at the onset of S-phase and peaking during mitosis.…”

Section: Introductionmentioning

confidence: 99%