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

作者：Wang, Luping; Wang, Panxia; Xu, Suowen; Li, Zhuoming; Duan, Dayue Darrel; Ye, Jiantao; Li, Jingyan; Ding, Yanqing; Zhang, Wenqing; Lu, Jing^*; Liu, Peiqing^*

来源：International Journal of Biological Sciences, 2022, 18(2): 783-799.

DOI：10.7150/ijbs.65211

• poly(ADP-ribosyl)ation
• C/EBP beta
• SUMOylation
• 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.

• 单位
  中山大学; 1