The present invention relates to mutated CSN5 polypeptides and their use in a method of screening modulators of CSN5 activity that could be used as therapeutic agents.

The present invention addresses the problem of providing a new means capable of modifying a protein material. According to the present invention, a protein material can be modified in property by causing a peptidylprolyl isomerase, or a peptidylprolyl isomerase and a protein modification enzyme to act on the protein material.

Methods for treating cardiovascular disease, and in particular heart failure, are provided comprising administering a therapeutically effective amount of a modulator of SERCA2a post-translation modification such as SUMOylation or acetylation. Also provided are methods of treating cardiovascular disease by inhibiting SERCA2a degradation. Further provided are methods of diagnosing a propensity to develop heart failure comprising determining if a SERCA2a mutant is present or determining the level of expression of SUMO1 in cardiomyocytes. The disclosure also provides methods of screening for therapeutics that modulate the post-translational modification of SERCA2a, such as by modulating post-translational SUMOylation and/or acetylation.

The present invention relates to mutated CSN5 polypeptides and their use in a method of screening modulators of CSN5 activity that could be used as therapeutic agents.

Methods for treating cardiovascular disease, and in particular heart failure, are provided comprising administering a therapeutically effective amount of a modulator of SERCA2a post-translation modification such as SUMOylation or acetylation. Also provided are methods of treating cardiovascular disease by inhibiting SERCA2a degradation. Further provided are methods of diagnosing a propensity to develop heart failure comprising determining if a SERCA2a mutant is present or determining the level of expression of SUMO1 in cardiomyocytes. The disclosure also provides methods of screening for therapeutics that modulate the post-translational modification of SERCA2a, such as by modulating post-translational SUMOylation and/or acetylation.

The present invention relates to polypeptides having deamidase inhibitor activity and polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.