The cross-talk between PARylation and SUMOylation in C/EBPβ at K134 site participates in pathological cardiac hypertrophy

Poly(ADP-ribosyl)ation (PARylation) and SUMO modification (SUMOylation) are novel post-translational modifications (PTMs) mainly induced by PARP1 and SUMO1. Growing evidence has revealed that C/EBP beta plays multiple roles in biological processes and participates in cardiovascular diseases. However, the cross-talk between C/EBP beta PARylation and SUMOylation during cardiovascular diseases is unknown. This study aims to investigate the effects of C/EBP beta PTMs on cardiac hypertrophy and its underlying mechanism. Abdominal aortic constriction (AAC) and phenylephrine (PE) were conducted to induce cardiac hypertrophy. Intramyocardial delivery of recombinant adenovirus (Ad-PARP1) was taken to induce PARP1 overexpression. In this study, we found C/EBP beta participates in PARP1-induced cardiac hypertrophy. C/EBP beta K134 residue could be both PARylated and SUMOylated individually by PARP1 and SUMO1. Moreover, the accumulation of PARylation on C/EBP beta at K134 site exhibits downregulation of C/EBP beta SUMOylation at the same site. Importantly, C/EBP beta K134 site SUMOylation could decrease C/EBP beta protein stability and participates in PARP1-induced cardiac hypertrophy. Taken together, these findings highlight the importance of the cross-talk between C/EBP beta PTMs at K134 site in determining its protein level and function, suggesting that multi-target pharmacological strategies inhibiting PARP1 and activating C/EBP beta SUMOylation would be potential for treating pathological cardiac hypertrophy.

Automated summary

This study investigates the crosstalk between C/EBP beta PARylation and SUMOylation during cardiac hypertrophy. The findings show that accumulation of PARylation on C/EBP beta at K134 site leads to downregulation of SUMOylation and contributes to cardiac hypertrophy. The study highlights the importance of the interaction between C/EBP beta PTMs, suggesting potential therapeutic strategies targeting PARP1 and activating C/EBP beta SUMOylation for treating cardiac hypertrophy.