Putting the Stress on UFM1 (Ubiquitin-Fold Modifier 1)

Defects in protein homeostasis (also known as proteostasis) are intrinsically
linked to age-related decline of cardiac function and likely contribute to
cardiomyopathies. Protein-folding chaperones and protein quality control
systems work overtime in the high stress cardiac environment, responding to wear
and tear. Tight regulation of the pathway components is often controlled by posttranslational
modifications. In addition to compact posttranslational modifications
such as phosphorylation, bulkier posttranslational modifications involve Ub (ubiquitin)
and other small UbL (Ub-like) proteins, which are covalently conjugated to
target proteins. These modifications can affect stability, localization, and function
of the target protein. Ufm1 (ubiquitin-fold modifier 1) is a less-studied UbL, but
modification by Ufm1 (ufmylation1) is emerging as an important mediator of the
endoplasmic reticulum (ER) stress response, which is activated in cardiomyocytes
during heart failure. Focusing on Ufl1 (Ufm1-ligase 1), one of the enzymes that
mediate ufmylation, the report from Li et al2 provide strong evidence that Ufl1 has
a cardioprotective role and points to the ufmylation pathway as a