SAK, A New Polo-Like Kinase, Is Transcriptionally Repressed by p53 and Induces Apoptosis upon RNAi Silencing - RNAi

SAK, A New Polo-Like Kinase, Is Transcriptionally Repressed by p53 and Induces Apoptosis upon RNAi Silencing
April 2005
Li, Jun; Tan, Mingjia; Li, Ling; Pamarthy, Deepika; Lawrence, Theodore S.; Sun, Yi
IngentaConnect
Abstract:
Chip profiling of a p53 temperature-sensitive tumor model identified SAK (Snk/Plk-akin kinase), encoding a new member of polo-like kinases (PLKs), as a gene strongly repressed by wild-type p53. Further characterization revealed that SAK expression was downregulated by wild-type p53 in several tumor cell models. Computer search of a 1.7-kb SAK promoter sequence revealed three putative p53 binding sites, but p53 failed to bind to any of these sites, indicating that SAK repression by p53 was not through a direct p53 binding to the promoter. Transcriptional analysis with luciferase reporters driven by SAK promoter deletion fragments identified SP-1 and CREB binding sites, which together conferred a two-fold SAK repression by p53. However, the repression was not reversed by cotransfection of SP-1 or CREB, suggesting a lack of interference between p53 and SP-1 or CREB. Significantly, p53-mediated SAK repression was largely reversed in a dose-dependent manner by Trichostatin A, a potent histone deacetylase (HDAC) inhibitor, suggesting an involvement of HDAC transcription repressors in SAK repression by p53. Biologically, SAK RNA interference (RNAi) silencing induced apoptosis, whereas SAK overexpression attenuated p53-induced apoptosis. Thus, SAK repression by p53 is likely mediated through the recruitment of HDAC repressors, and SAK repression contributes to p53-induced apoptosis.
Keywords: APOPTOSIS; P53; POLO-LIKE KINASE; RNAI SILENCING; TRANSCRIPTION REPRESSION
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