E3 Ubiquitin Ligase ASB14 Inhibits Cardiomyocyte Proliferation by Regulating MAPRE2 Ubiquitination

Yanpeng Yang; Dongpu Ma; Bo Liu; Xu Sun; Wei Fu; Feifei Lv; Chunguang Qiu

doi:10.1007/s12013-024-01223-x

E3 Ubiquitin Ligase ASB14 Inhibits Cardiomyocyte Proliferation by Regulating MAPRE2 Ubiquitination

Cell Biochem Biophys. 2024 Feb 6. doi: 10.1007/s12013-024-01223-x. Online ahead of print.

Authors

Yanpeng Yang¹, Dongpu Ma², Bo Liu², Xu Sun³, Wei Fu⁴, Feifei Lv², Chunguang Qiu⁵

Affiliations

¹ Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
² Cardiac Care Unit, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China.
³ Department of Integrated Chinese and Western Medicine, Henan Cancer Hospital and Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China.
⁴ Tuberculosis Department No. 1 Ward, Henan Provincial Chest Hospital, Zhengzhou University, Zhengzhou, China.
⁵ Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. qiuchunguang2013@126.com.

PMID: 38319584
DOI: 10.1007/s12013-024-01223-x

Abstract

The ubiquitin proteasome system is a highly specific and selective protein regulatory system that plays an essential role in the regulation of the cell cycle. Despite its significance, the role of ubiquitination in cardiomyocyte proliferation remains largely unclear. This study aimed to investigate the potential impact of E3 ubiquitin ligase ASB14 (Ankyrin Repeat And SOCS Box Containing 14) on cardiac regeneration. We conducted a microarray analysis of apical resection ventricle tissues, and our findings revealed that ASB14 was down-regulated during the cardiac regenerative response. Subsequently, we examined the effect of ASB14 silencing on cardiomyocyte nuclear proliferation both in vitro and in vivo. Our results indicated that ASB14 silencing promoted cardiomyocyte nuclear proliferation, suggesting that ASB14 may play a role in regulating cardiac regeneration. To further investigate the potential therapeutic implications of ASB14 deficiency, we examined the cardiac function of mice with ASB14 deficiency in response to ischemic injury. Our findings showed that mice with ASB14 deficiency exhibited preserved cardiac function and a therapeutic effect in response to ischemic injury, which was attributed to the enhancement of cardiomyocyte nuclear proliferation. To elucidate the underlying mechanisms, we investigated the effect of ASB14 on microtubule-associated protein RP/EB family member 2 (MAPRE2) protein degradation. Our results indicated that the loss of ASB14 decreased the degradation of MAPRE2 protein, subsequently promoting cardiomyocyte nuclear proliferation and enhancing cardiac repair after myocardial infarction (MI). In conclusion, our study provides evidence that inhibition of ASB14-mediated MAPRE2 ubiquitination promotes cardiomyocyte nuclear proliferation, which may serve as a potential target for treating heart failure induced by MI injury.

Keywords: ASB14; Cardiac regeneration; MAPRE2; Myocardial infarction; Ubiquitination.