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Dual promoter regulation of death-associated protein kinase gene leads to differentially silenced transcripts by methylation in cancer.


ABSTRACT: Death-associated protein kinase (DAPK), a mediator of apoptotic systems, is silenced by promoter hypermethylation in lung and breast tumors. This gene has a CpG island extending 2500 bp from the translational start site; however, studies characterizing its transcriptional regulation have not been conducted. Two transcripts for DAPK were identified that code for a single protein, while being regulated by two promoters. The previously identified DAPK transcript designated as exon 1 transcript was expressed at levels 3-fold greater than the alternate exon 1b transcript. Deletion constructs of promoter 1 identified a 332 bp region containing a functional CP2-binding site important for expression of the exon 1 transcript. While moderate reporter activity was seen in promoter 2, the region compr

SUBMITTER: Pulling LC 

PROVIDER: S-EPMC2792322 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature