The deubiquitinase USP5 prevents accumulation of protein aggregates in cardiomyocytes

Protein homeostasis is crucial for maintaining cardiomyocyte (CM) function. Disruption of proteostasis results in accumulation of protein aggregates causing cardiac pathologies such as hypertrophy, dilated cardiomyopathy (DCM), and heart failure. Here, we identify the ubiquitin-specific peptidase 5 (USP5) as a critical determinant of protein quality control (PQC) in CM. CM-specific loss of mUsp5 leads to the accumulation of polyubiquitin chains and protein aggregates, cardiac remodeling, and eventually DCM. USP5 interacts with key components of the proteostasis machinery, including PSMD14 and absence of USP5 increases activity of the ubiquitin-proteasome system and autophagic flux in CMs. Cardiac-specific hUSP5 overexpression reduces pathological remodeling in pressure-overloaded mouse hearts and attenuates protein aggregate formation in titinopathy and desminopathy models. Since CMs from humans with end-stage DCM show lower USP5 levels and display accumulation of ubiquitinated protein ..., , , # Data from: The deubiquitinase USP5 prevents accumulation of protein aggregates in cardiomyocytes

[https://doi.org/10.5061/dryad.1c59zw462](https://doi.org/10.5061/dryad.1c59zw462)

## Description of the data and file structure

The Excel files contain the raw data used for statistical analysis and graph generation in the main and supplementary figures of the manuscript, 'The deubiquitinase USP5 prevents accumulation of protein aggregates in cardiomyocytes'. The methods used to generate the data are described in the manuscript. Each tab in the Excel sheet refers to an individual panel in the respective figures.

### Files and variables

#### File: Eibach\_et\_al.\_R1\_Source\_Data\_Main\_Figures.xlsx

**Description:**  Raw data for individual figure panels for different figures in the main manuscript. 

**Source Data Main Figures**

Data for main figures are summarized in a single excel file containing different tabs for different datasets.

Figure 1D: This tab contains concentrations...