Figure 11.

Model for the proposed role of Pim-1 and HBP1 in the response to H₂O₂-induced premature senescence and apoptosis. In response to H₂O₂ induction, Pim-1 can positively regulate HBP1 by binding and phosphorylating at the position of Ser-372/Ser-380. This leads to HBP1 activation, which selectively turns on Pim-1 transcription, resulting in up-regulation of the Pim-1 level and further stabilization and induction of HBP1. The potent HBP1 activation leads to regulation of many other HBP1 target genes, including p16, DNMT1, and Bax, thus inducing premature senescence and apoptosis.