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. 2017 Mar 14;16:60. doi: 10.1186/s12943-017-0611-1

Fig. 3.

Fig. 3

Cdk5 takes part in DDR through STAT3 pathway. In growing cancer cells, the constitutive activation of STAT3 via JAK-mediated phosphorylation on tyrosine 705 allows the nuclear translocation and DNA binding of STAT3 and up-regulation of cyclin D1 gene and myc gene, leading to cell cycle activation and proliferation. When cells are treated with topoisomerase I inhibitor (a DNA damaging agent), the activation of STAT3 by JAK is inhibited, while the expression and activity of Cdk5 are increased in response to DNA damaging agent. Up-regulated Cdk5 associates with STAT3 and phosphorylates it on serine 727, leading to activation of STAT3. The activated STAT3 then translocates to nucleus and interacts with the promoter of Eme1 gene, promoting the rescue of broken replication forks caused by DNA damage