DNA protein interaction, protein p53, regulation of protein activity

Tumour supressor protein p53 represents one of the most important factors regulating cell proliferation, diferentiation and programmed cell death. P53 triggers growth arrest or apoptosis in response to different cellular stress signals and its biochemical function is associated with the ability to operate as a transcription factor. The way of p53 activation seems to be the critical event responsible for the p53 response to DNA damage. The most likely physiological mechanism of p53 activation to sequence-specific DNA binding is its post-translational modification. Using non-radioactive EMSA we show that phosphorylation of p53 protein with CKII at Ser392, PKC at Ser378 and cdk2/cyclinA at Ser315 can efficiently activate p53 to sequence-specific DNA binding in vitro. In addition, p53 co-phosphorylation with cdk2/cyclinA and PKC or cdk2/cyclinA and CKII increase the DNA binding activity of p53 but, in contrast, co-phosphorylation with PKC and CKII results in the decrease of the p53-DNA binding.