Modulation of the Human Protein Kinase Cα Gene Promoter by Activator Protein-2

Clark, Joannah Hackenbruck; Haridasse, Vedanandam; Glazer, Robert I.

doi:10.1021/bi025600k

Cited by 14 publications

(10 citation statements)

References 42 publications

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“…However, neither an siRNA against AML1 (decreasing the level of AML1 mRNA by up to 60%) nor a mutation of the putative AML1-binding site had any effect on the level of mRNA encoding PKCα or on PKCα (-227 to +77)-dependent luciferase activity, indicating that SOX9-dependent PKCα repression is not mediated through a similar AML1-dependent mechanism (data not shown). The PKCα promoter, however, does exhibit a functional SP1-binding site (Clark et al, 2002) (Fig. 4A), and previous GSTpulldown data from Wissmuller et al indicate that SP1 is able to interact with the SOXE members SOX8 and SOX10 (Wissmuller et al, 2006).…”

Section: Sox9-dependent Pkcα Repression Involves Sp1supporting

confidence: 75%

A new mechanism of SOX9 action to regulate PKCα expression in the intestine epithelium

Dupasquier

Abdel-Samad

Glazer

et al. 2009

Journal of Cell Science

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Variations of protein kinase C (PKC) expression greatly influence the proliferation-to-differentiation transition (PDT) of intestinal epithelial cells and might have an important impact on intestinal tumorigenesis. We demonstrate here that the expression of PKCα in proliferating intestinal epithelial cells is repressed both in vitro and in vivo by the SOX9 transcription factor. This repression does not require DNA binding of the SOX9 high-mobility group (HMG) domain but is mediated through a new mechanism of SOX9 action requiring the central and highly conserved region of SOXE members. Because SOX9 expression is itself upregulated by Wnt-APC signaling in intestinal epithelial cells, the present study points out this transcription factor as a molecular link between the Wnt-APC pathway and PKCα. These results provide a potential explanation for the decrease of PKCα expression in colorectal cancers with constitutive activation of the Wnt-APC pathway.

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Section: Sox9-dependent Pkcα Repression Involves Sp1supporting

confidence: 75%

A new mechanism of SOX9 action to regulate PKCα expression in the intestine epithelium

Dupasquier

Abdel-Samad

Glazer

et al. 2009

Journal of Cell Science

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“…For example, sequence AP-2 (activator protein 2, caCCCCggggcc; ref. 19), common to the 5Ј UTR of some of our inhibited genes, was altered in Rpp38, Rpp29, Rpp25, and Rpp21. Other similar comparisons also showed up but did not have the same correlation with these four …”

Section: Is There a Common Means Of Gene Regulation?mentioning

confidence: 89%

Coordinate inhibition of expression of several genes for protein subunits of human nuclear RNase P

Kovrigina

Wesolowski

Altman

2003

Proc. Natl. Acad. Sci. U.S.A.

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The deliberate inhibition of expression of one of the protein subunits (Rpp38) of human nuclear RNase P is achievable by using external guide sequence (EGS) technology. Both the protein product and the mRNA are greatly reduced 24 h after transient transfection with a gene coding for an appropriate EGS. Control experiments indicated that four other protein subunits of RNase P and their RNAs are also inhibited with no external manipulation. The remaining RNase P proteins, their mRNAs, and the RNA subunit of RNase P all are unchanged. Several short nucleotide sequences adjacent to the ORFs for the inhibited genes are similar and could be targets for transcriptional repression. The explanation of coordinate inhibition of the expression of the product of one particular gene by the transfection of an EGS (or RNA interference) requires some care in terms of interpreting phenotypic effects because, in our case, several gene products that are not targeted are also inhibited.external guide sequences ͉ upstream sequences ͉ downstream sequences ͉ Rpp38T he regulation of expression of single genes in human cells by external manipulation is an important problem. RNA interference, the use of antisense RNA, and similar methods (1, 2) have been used with moderate success on cells in tissue culture. One other method, which uses RNase P as the agent that cleaves targeted RNAs, is also quite promising (3, 4). In the past, this mechanism has been used, for example, to decrease the amount of viral infection by regulating certain essential viral genes (5). This method, which uses external guide sequences (EGSs), has now been used to regulate expression of a gene that encodes one of the protein subunits of RNase P.Human nuclear RNase P has at least 10 protein subunits and one RNA subunit and is localized in the nuclei of cells (6-8). While using EGS action to study the expression of one of the subunits, Rpp38, we did not know whether any of the other proteins would also be affected. In fact, the mechanism for the control of several genes simultaneously in human cells is a diverse and puzzling problem. After surveying cells after transient transfection with a plasmid that harbored EGS Rpp38 by Western and Northern blots, we found an expected decrease in both the mRNA and translation product of Rpp38. As controls, we also explored the amounts of mRNA and protein made by other subunits of RNase P. Four other genes were inhibited, whereas the rest were unchanged. This finding led to an examination of what factors in terms of upstream and downstream DNA and RNA sequences were involved with this phenomenon and whether there could be a common regulatory feature. Materials and MethodsConstruction of EGSs and Plasmids. A DNA fragment that contains the Rpp38 cDNA under control of a T7 promoter was obtained by PCR using the full-length Rpp38 cDNA clone F3053 in PCR-Script-Amp (kindly provided by C. C. Liew, University of Toronto, Toronto) as a template. Primer oligonucleotides were P38F5 5Ј-TAA TAC GAC TCA CTA TAG GGC TCA AGT TATC-3Ј and P38BHIR ...

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“…This promoter does not have a TATA box. 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).…”

Section: Discussionmentioning

confidence: 99%

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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Modulation of the Human Protein Kinase Cα Gene Promoter by Activator Protein-2

Cited by 14 publications

References 42 publications

A new mechanism of SOX9 action to regulate PKCα expression in the intestine epithelium

A new mechanism of SOX9 action to regulate PKCα expression in the intestine epithelium

Coordinate inhibition of expression of several genes for protein subunits of human nuclear RNase P

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

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