Fig. 6: Hyperglycaemia induces cell apoptosis via the TRIM21-FOXD1-BCL-2 signalling axis.
From: The TRIM21-FOXD1-BCL-2 axis underlies hyperglycaemic cell death and diabetic tissue damage
Chronic hyperglycaemia induces the expression of the ubiquitin E3 ligase TRIM21, which polyubiquitinates the transcription factor FOXD1 to control its protein stability, leading to hyperglycaemia-triggered downregulation of FOXD1 proteins. FOXD1 promotes the transcription of the antiapoptotic gene BCL-2 by directly binding to the BCL-2 promoter. Accordingly, hyperglycaemia-triggered degradation of FOXD1 mediated by TRIM21 shifts the balance between proapoptotic and antiapoptotic proteins and initiates apoptosis and tissue injury.
