Ufm1 is a rarely studied ubiquitin-like protein. While Ufm1 modification (ufmylation) is essential for embryonic development and mutations in ufmylation are linked to multiple human diseases, little is known about its pathophysiological significance in the heart. We found that dysregulation of ufmylation is associated with hypertrophic, dilated, and ischemic cardiomyopathies. We were the first that identified ufmylation as a crucial mechanism regulating cardiac and ER homeostasis.
As an important post translational modification, ubiquitination virtually regulates every aspect of cellular processes. Deubiquitinases (DUBs), which reverse the process of ubiquitination, are important regulators of the ubiquitin system. There are approximately 100 deubiquitinases encoded by the human genome, of which little is known about their biological functions in the heart. Using both gain- and loss-of-function approaches, we aim to determine the functional importance of these DUBs in the heart.
Liu J, Wen T, Dong K, He X, Zhou H, Shen J, Fu Z, Hu G, Ma W, Li J, Wang W, Wang L, Akerberg BN, Xu J, Osman I, Zheng Z, Wang W, Du Q, Pu WT, Xiang M, Chen W, Su H, Zhang W, Zhou J. TEAD1 protects against necroptosis in postmitotic cardiomyocytes through regulation of nuclear DNA-encoded mitochondrial genes. Cell Death Differ. 2021 Jan 19. doi: 10.1038/s41418-020-00732-5. PMID: 33469230
