The repressive role of p53 on the human mitotic centromere-associated kinesin (MCAK) core promoter from ‒266 to +54, relative to the transcription start site, has been determined. The MCAK mRNA and protein levels were 2.1- and 3.0-fold higher, respectively, in HCT116 (p53‒/‒) than in HCT116 (p53+/+) cells. Enforced down-regulation of p53 levels either in HCT116 (p53+/+) cells by p53 RNAi treatment or in MCF-7 cells using shRNA for p53 (shp53) resulted in a remarkable increase in the MCAK protein level. Site-directed mutagenesis and ChIP analyses showed that p53-mediated repression of the MCAK core promoter activity was not directly exerted by p53-binding to putative p53-response elements (p53-RE1 at -173/-166 and p53-RE2 at -245/-238), but indirectly by attenuating Sp1 binding to GC-motifs (GC1 at -93/-84 and GC2 at -119/-110). Treatment of HEK-293 cells bearing the MCAK core promoter-reporter (pGL2-320-Luc) with mithramycin A, which down-regulates Sp1 gene expression, reduced the promoter activity as well as endogenous MCAK levels. Exposure of HCT116 (p53+/+) cells to nutlin-3a, a validated activator of p53, caused a simultaneous reduction in Sp1 and MCAK protein levels, but not in HCT116 (p53-/-) cells. In contrast to wild-type (wt)-p53, tumor-derived p53 mutants (p53V143A, p53R248W, and p53R273H) failed to repress the Sp1-dependent activation of the MCAK promoter and to down-regulate endogenous levels of Sp1 and MCAK proteins. Collectively, these findings demonstrate that p53 can repress MCAK promoter activity indirectly via down-regulation of Sp1 expression level, and suggest that MCAK elevation in human tumor cells might be due to p53 mutation.
Pubmed ID: 29244835 RIS Download
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View all literature mentionsTESS is a web tool for predicting transcription factor binding sites in DNA sequences. It can identify binding sites using site or consensus strings and positional weight matrices from the TRANSFAC, JASPAR, IMD, and our CBIL-GibbsMat database. You can use TESS to search a few of your own sequences or for user-defined CRMs genome-wide near genes throughout genomes of interest. Search for CRMs Genome-wide: TESS now has the ability to search whole genomes for user defined CRMs. Try a search in the AnGEL CRM Searches section of the navigation bar.. You can search for combinations of consensus site sequences and/or PWMs from TRANSFAC or JASPAR. Search DNA for Binding Sites: TESS also lets you search through your own sequence for TFBS. You can include your own site or consensus strings and/or weight matrices in the search. Use the Combined Search under ''Site Searches'' in the menu or use the box for a quick search. TESS assigns a TESS job number to all sequence search jobs. The job results are stored on our server for a period of time specified in the search submit form. During this time you may recall the search results using the form on this page. TESS can also email results to you as a tab-delimited file suitable for loading into a spreadsheet program. Query for Transcription Factor Info: TESS also has data browsing and querying capabilities to help you learn about the factors that were predicted to bind to your sequence. Use the Query TRANSFAC or Query Matrices links above or use the search interface provided from the home page.
View all literature mentionsSoftware for automatic general image analysis. It provides fully automatic analysis of 1-D gels including lane creation, background subtraction, band detection, molecular weight calibration, quantity calibration, and normalization. Editing tools are provided for cropping, rotating, and filtering images.
View all literature mentionsCell line SW480 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HCT 116 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HeLa is a Cancer cell line with a species of origin Homo sapiens
View all literature mentionsCell line MCF-7 is a Cancer cell line with a species of origin Homo sapiens (Human)
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