Figure 8.

CDK9–cyclin T1 complex activates ATF4 activity through multiple phosphorylations under ER stress, leading to vascular calcification in CKD. The proposed mechanism of CHOP induction by ATF4 with CDK9–cyclin complexes in vascular calcification is shown. CKD increases levels of C18:0. C18:0 activates the PERK–eIF2α–ATF4–CHOP axis of ER stress signaling, resulting in calcification. The CDK9–cyclin T1 complex phosphorylates and mediates translocation of ATF4 to the ATF4RE of the CHOP promoter, and cyclins T2/K compete with cyclin T1 for binding with CDK9.