Regulation of BECN1-Mediated Autophagy by HSPB6: Insights from A Human HSPB6S10F Mutant
Year: 2017
Type: dataset
Abstract: HSPB6/Hsp20 (heat shock protein family B [small] member 6) has emerged as a novel cardioprotector against stress-induced injury. We identified a human mutant of HSPB6 (HSPB6S10F) exclusively present in dilated cardiomyopathy (DCM) patients. Cardiac expression of this mutant in mouse hearts resulted in remodeling and dysfunction, which progressed to heart failure and early death. These detrimental effects were associated with reduced interaction of mutant HSPB6S10F with BECN1/Beclin 1, leading to BECN1 ubiquitination and its proteosomal degradation. As a result, autophagy flux was substantially inhibited and apoptosis was increased in HSPB6S10F-mutant hearts. In contrast, overexpression of wild-type HSPB6 (HSPB6 WT) not only increased BECN1 levels, but also competitively suppressed binding of BECN1 to BCL2, resulting in stimulated autophagy. Indeed, preinhibition of autophagy attenuated the cardioprotective effects of HSPB6 WT. Taken together, these findings reveal a new regulatory mechanism of HSPB6 in cell survival through its interaction with BECN1. Furthermore, Ser10 appears to be crucial for the protective effects of HSPB6 and transversion of this amino acid to Phe contributes to cardiomyopathy.
Source: Figshare
Authors: Liu, Guan-Sheng, Zhu, Hongyan, Cai, Wen-Feng, Wang, Xiaohong, Jiang, Min, Essandoh, Kobina, Vafiadaki, Elizabeth, Haghighi, Kobra, Lam, Chi Keung, Gardner, George, Adly, George, Nicolaou, Persoulla, Sanoudou, Despina, Liang, Qiangrong, Rubinstein, Jack, Fan, Guo-Chang, Kranias, Evangelia G.
Institutions: Nantong University, Harvard University, China Medical University, Florida International University, Massachusetts General Hospital, Binzhou Medical College Hospital, Ningxia Medical University General Hospital, Tang Du Hospital, First Affiliated Hospital of Harbin Medical University, Nanjing Medical University, China Medical University, Tsinghua University, Air Force Medical University, Jiangnan University, Fujian University of Traditional Chinese Medicine, Nanjing Agricultural University, Nanjing Tech University, Xinjiang Medical University, Shanghai University of Finance and Economics, Sichuan University, Shenzhen Center for Disease Control and Prevention, First Affiliated Hospital of Soochow University, University of Cincinnati
Language: English
Topic: Heat shock proteins research
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W4394383899