Expression of PACT is regulated by Sp1 transcription factor

Fasciano, Stephen; Kaufman, Amanda R.; Patel, Rekha C.

doi:10.1016/j.gene.2006.10.003

Cited by 13 publications

(5 citation statements)

References 57 publications

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“…Sp1 is crucial for basal transcription of KLF5 , DRG2 and PRKRA . 24 , 25 , 26 We confirmed that TRA2β4 knockdown significantly increased the expression of these mRNAs in HCT116 cells, suggesting that interactions between TRA2β4 and Sp1 may be able to significantly alter the gene expression program.…”

Section: Discussionsupporting

confidence: 63%

Ultraconserved region-containing Transformer 2β4 controls senescence of colon cancer cells

et al. 2016

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Ultraconserved regions (UCRs) are >200 bp genomic segments with perfect human-to-rodent sequence identity. Transcribed UCRs constitute a new category of noncoding RNAs whose functions remain poorly understood. The human transformer 2β (TRA2B) gene contains a 419-bp UCR spanning the 276-bp exon 2 and its neighboring introns. TRA2B exon 2 has premature stop codons, whereas an exon 2-containing splice variant (TRA2β4) was expressed preferentially in the nuclei of human colon cancer cells. TRA2β4 knockdown p53-independently stimulated CDKN1A transcription and increased p21, resulting in the appearance of senescent cells. Biotin pull-down and RNA immunoprecipitation assays revealed that TRA2β4 interacted with Sp1 through a Sp1-binding sequence (485-GGGG-488) in a stem-loop structure of exon 2. Mutation of this sequence (485-AAGG-488) disrupted the stem-loop structure, blocked the interaction with Sp1 and increased CDKN1A transcription. Overexpression of TRA2β4 significantly decreased CDKN1A mRNA levels and accelerated cell growth, but the introduction of the mutation in the Sp1-binding sequence completely canceled these effects. Taken together, TRA2β4 may sequester Sp1 from occupying promoters of target genes including CDKN1A, promoting cell growth by interrupting the senescence-related gene expression program. This novel function of TRA2β4 may uncover an oncogenic function of transcribed UCRs.

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Section: Discussionsupporting

confidence: 63%

Ultraconserved region-containing Transformer 2β4 controls senescence of colon cancer cells

et al. 2016

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“…Induction of PACT expression upon Tunicamycin treatment was inhibited by actinomycin D, thus confirming that ER stress increases PACT expression at the mRNA level. The exact mechanisms triggering PACT gene expression remains to be determined, but it is already known that the expression of PACT is regulated by the SP1 transcription factor (12), and that ER stress pathways induced by tunicamycin or thaspigargin can activate SP transcription factors, including SP1 protein (1). It is not yet clear whether SP1 mRNA and protein levels are increased or not in AD brains (7, 29).…”

Section: Discussionmentioning

confidence: 99%

The PKR Activator PACT Is Induced by Aβ: Involvement in Alzheimer's Disease

Paquet¹,

Mouton-Liger

Meurs

et al. 2011

Brain Pathology

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The neuropathological hallmarks of Alzheimer's disease (AD) include senile plaques made of Aβ peptide, neurofibrillary tangles containing hyperphosphorylated tau protein and neuronal loss. The pro-apoptotic kinase PKR can be activated by Aβ and can phosphorylate tau protein via GSK3β kinase activation. The activated form of PKR (pPKR) accumulates in affected neurons and could participate in neuronal degeneration in AD. The mechanism of abnormal PKR activation in AD is not elucidated but could be linked to the PKR activator PACT. PACT stainings, and levels were assessed in the brains of AD patients and in APP/PS1 knock-in transgenic mice and in cell cultures exposed to stresses. We showed that PACT and pPKR colocalizations are enhanced in AD brains. Their levels are increased and correlated in AD and APP/PS1 knock-in mice brains. In human neuroblastoma cells exposed to Aβ, tunicamycin or H2O2, PACT and pPKR concentrations are increased. PACT then PKR inhibitions indicate that PACT is upstream of PKR activation. Our findings demonstrate that PACT levels are enhanced in AD brains and could partly be caused by the action of Aβ. In addition, PACT participates in PKR activation. The PACT-PKR pathway represents a potential link between Aβ accumulation, PKR activation and tau phosphorylation.

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“…To verify that SP1 binds to the immediate upstream region of the CCL5 promoter in native chromatin, ChiP assay was used (40). SP1 Ab was used to immunoprecipitate the CCL5 promoter DNA from YT cells.…”

Section: Sp1 Binds In Vivo Near the Tata Box On The Ccl5 Promotermentioning

confidence: 99%

JNK MAPK Pathway Regulates Constitutive Transcription of CCL5 by Human NK Cells through SP1

Kumar

Hosse

Toerne

et al. 2009

The Journal of Immunology

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N atural killer cells have features similar to CD8 ϩ T cells in that they recognize and lyse virally infected and neoplastic cells; express receptors such as CD28, CD43, and 2B4; and contain cytolytic granules (1-6). The activation of NK surface receptors triggers microtubule organization, granule polarization, and cytotoxicity signals through both ERK2 and JNK1 phosphorylation pathways (7,8).The chemokine CCL5 has been suggested to act as an important mediator of diverse inflammatory processes (9 -11). In CTL, the protein is associated with the development and expression of effector function (12)(13)(14). In CD8 ϩ T cells, CCL5 transcription occurs late (3-5 days) after the activation of naive cells and is coincident with the up-regulation of perforin, the granzymes, and granulysin (15)(16)(17). A complex of nuclear proteins recruited to the promoter by Krü ppel-like factor 13 (KLF13) 3 controls the transcription of CCL5 in CTL (18,19). KLF13 is translationally regulated and appears several days after T cell activation. The p38 and ERK1/2 MAPK pathways control KLF13 gene expression, whereas pre-mRNA processing factor 4 homolog B, a member of the MAPK family, regulates KLF13 phosphorylation in T cells and by extension CCL5 expression (20,21). In NK cells, the MAPKs and PI3K pathways are also involved in triggering the polarized release of cytolytic granules (7,8,(22)(23)(24); however, the role of these pathways in the control of CCL5 expression in NK cells has not been investigated.We report in this study that unlike in T cells, CCL5 mRNA is constitutively transcribed and translated in peripheral blood NK cells. The CCL5 protein is localized to secretory vesicles that are distinct from the cytolytic granules. The constitutive transcription of CCL5 mRNA in NK cells is mediated through binding of the SP1 transcription factor to a site just upstream from the TATA box of the CCL5 gene. The JNK/MAPK pathway in turn controls SP1 expression and, through this, constitutive CCL5 transcription. Materials and Methods Abs, inhibitors, and oligonucleotidesPhospho-specific Abs that recognize the activated forms of phospho-stressactivated protein kinase/JNK (Thr 183 /Tyr 185 ) and inactive forms of stressactivated protein kinase/JNK were purchased from Cell Signaling Technology (catalog 9251 and 9252). The Abs for NF-B, p50, p52, p65, SP1, and SP3 were purchased from Upstate Biotechnology (catalog 06-886, 06-413, 06-418, 07-645, and 07-107, respectively), and ␤ actin for proteinloading control and KLF13 was purchased from Abcam (catalog ab8227 and ab1127). Primary Abs were as follows: mouse IgG2b-anti-human CCL5 VL1 or VL2 hybridoma supernatant (25), mouse IgG1 anti-human granzyme B (Serotec; catalog MCA2120PE), mouse anti-human perforin (BD Biosciences; catalog 556434), goat anti-mouse IgG1 CD3 Pacific Blue (DakoCytomation; PB982), goat anti-mouse IgG1 CD56 allophycocyanin conjugated (BD Biosciences; catalog IM2474), and rabbit anti-human CD8 (Neomarkers; catalog RM-9116-R7 The costs of publication of this article were defray...

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Expression of PACT is regulated by Sp1 transcription factor

Cited by 13 publications

References 57 publications

Ultraconserved region-containing Transformer 2β4 controls senescence of colon cancer cells

Ultraconserved region-containing Transformer 2β4 controls senescence of colon cancer cells

The PKR Activator PACT Is Induced by Aβ: Involvement in Alzheimer's Disease

JNK MAPK Pathway Regulates Constitutive Transcription of CCL5 by Human NK Cells through SP1

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