Figure 8.

Model for the regulation of PDX1.2 and vitamin B₆ sustenance under heat stress. Under normal conditions (left panel), HSFA1 is bound to HSP70. The PDX1.2 gene is depicted as in Figure 6 and has two transcriptional start sites. TSS1 is used under these conditions, which is within the HSE. TSS2 is not used. A catalytic PDX1 (cPDX1) maintains PLP homeostasis. It is not clear if there is minor stabilization of cPDX1 by the basal expression of PDX1.2 under normal conditions. Under heat stress conditions (right panel), unfolded proteins (UPr) compete for HSP70, leaving HSFA1 free to bind to the HSE in PDX1.2. TSS2 is used under these conditions, leading to strong induction of PDX1.2 expression (thick black arrow). The induction of PDX1.2 appears to stabilize cPDX1 under these circumstances, thereby contributing to PLP homeostasis. Both cPDX1 and PLP homeostasis could be compromised under heat stress conditions (gray dashed lines) but are “protected” by the induction of PDX1.2 expression.