Small Ubiquitin Modifier (SUMO) signaling and muscle biology
The research group Small Ubiquitin Modifier (SUMO) signaling and muscle biology is lead by Stefano Gastaldello and located with the Department of Physiology and Pharmacology.
SUMO, the Small Ubiquitin-like Modifier is a 101-amino acid protein that can be covalently attached to lysine residues on target proteins via an enzymatic cascade reaction named SUMOylation. SUMOylation requires E1 (hetero-dimer SUMO-activating, SAE1/2), E2 (SUMO-specific conjugating, Ubc9), and, in most cases, E3 (SUMO ligase, PIASs) enzymes, see Figure 1 below.
SUMOylation is an important post-translational modification that regulates protein functions and contributes to several intracellular process including transcription, DNA repair, chromatin remodeling, signal transduction, etc. Particularly, various stress conditions are known to promote global changes in the SUMO signaling, both in cell cultures and at the organs level. Moreover, defect on the SUMOylation machinery have been associated with severe diseases such as neurodegeneration, muscle atrophy, cancer and heart failure.
Our major contribution towards the muscle physiology field is to identify new skeletal muscle proteins targeted by SUMO in normal muscle activity and in muscle disorders. The identification of numerous key regulatory proteins, which functions are controlled by SUMO modification and undergo to a global/massive changes in SUMOylation status, may predict the state of the disease and provide useful information for muscle disorders diagnosis, progression and prognosis.
We aim also to characterize the underlying mechanisms of the up/down-stream signals that regulate expression and activity of SUMO enzymes since they will provide new useful information on SUMO muscle physiology and suggest novel approaches to manipulate SUMOylation in order to combat muscle diseases.
Figure 2: Diaphragm muscle fibers are differently stained with antibodies to SUMO1 and SUMO2/3. Consecutive serial muscle sections were subjected to NADH-TR staining to recognize the oxidative (dark purple) and glycolytic (light purple) fibers and to ATPase (pH 10.3) staining to distinguish type I (white) and type II (black) fibers. Venn diagram comparison between SUMO1 (red circle) and SUMO2 (green circle) identified proteins from control diaphragm. For details, see the article by Arvind Venkat Namuduri A.V., et al., Mol Cell Proteomics. 2017 Apr 3.