%0 Journal Article %T Glycogen synthase kinase3 beta phosphorylates serine 33 of p53 and activates p53's transcriptional activity %A Gaetan A Turenne %A Brendan D Price %J BMC Cell Biology %D 2001 %I BioMed Central %R 10.1186/1471-2121-2-12 %X The 2 isoforms of GSK3, GSK3¦Á and GSK3¦Â, phosphorylate the sequence Ser-X-X-X-Ser(P) when the C-terminal serine residue is already phosphorylated. Several p53 kinases were examined for their ability to create GSK3 phosphorylation sites on the p53 protein. Our results demonstrate that phosphorylation of serine 37 of p53 by DNA-PK creates a site for GSK3¦Â phosphorylation at serine 33 in vitro. GSK3¦Á did not phosphorylate p53 under any condition. GSK3¦Â increased the transcriptional activity of the p53 protein in vivo. Mutation of either serine 33 or serine 37 of p53 to alanine blocked the ability of GSK3¦Â to regulate p53 transcriptional activity. GSK3¦Â is therefore able to regulate p53 function in vivo. p53's transcriptional activity is commonly increased by DNA damage. However, GSK3¦Â kinase activity was inhibited in response to DNA damage, suggesting that GSK3¦Â regulation of p53 is not involved in the p53-DNA damage response.GSK3¦Â can regulate p53's transcriptional activity by phosphorylating serine 33. However, GSK3¦Â does not appear to be part of the p53-DNA damage response pathway. Instead, GSK3¦Â may provide the link between p53 and non-DNA damage mechanisms for p53 activation.The p53 tumor suppressor gene is activated during several cellular processes. These include DNA damage caused by Ionizing Radiation and genotoxic agents [1], by expression of activated oncogenes such as ras or myc [2], or during progression of primary cells to senescence [3]. The activation of p53 by these diverse stimuli can initiate either growth arrest or apoptosis depending on the cellular context [1,2,3]. p53 posses sequence-specific DNA binding activity and functions in the cell as a transcriptional regulator. Many p53 regulated genes have been identified [3,4,5], and the majority of the cellular effects of p53 activation can be attributed to the activation of these p53 target genes.The mechanism of p53 activation in response to either DNA damage or oncogene expression occurs through sta %U http://www.biomedcentral.com/1471-2121/2/12