| First Author | Xie X | Year | 2019 |
| Journal | Sci Adv | Volume | 5 |
| Issue | 5 | Pages | eaau0495 |
| PubMed ID | 31086810 | Mgi Jnum | J:288680 |
| Mgi Id | MGI:6430048 | Doi | 10.1126/sciadv.aau0495 |
| Citation | Xie X, et al. (2019) The immunoproteasome catalytic beta5i subunit regulates cardiac hypertrophy by targeting the autophagy protein ATG5 for degradation. Sci Adv 5(5):eaau0495 |
| abstractText | Pathological cardiac hypertrophy eventually leads to heart failure without adequate treatment. The immunoproteasome is an inducible form of the proteasome that is intimately involved in inflammatory diseases. Here, we found that the expression and activity of immunoproteasome catalytic subunit beta5i were significantly up-regulated in angiotensin II (Ang II)-treated cardiomyocytes and in the hypertrophic hearts. Knockout of beta5i in cardiomyocytes and mice markedly attenuated the hypertrophic response, and this effect was aggravated by beta5i overexpression in cardiomyocytes and transgenic mice. Mechanistically, beta5i interacted with and promoted ATG5 degradation thereby leading to inhibition of autophagy and cardiac hypertrophy. Further, knockdown of ATG5 or inhibition of autophagy reversed the beta5i knockout-mediated reduction of cardiomyocyte hypertrophy induced by Ang II or pressure overload. Together, this study identifies a novel role for beta5i in the regulation of cardiac hypertrophy. The inhibition of beta5i activity may provide a new therapeutic approach for hypertrophic diseases. |
