Simon Sipen Wing, McGill University
Endocrinology & Metabolism
Professor
Montreal, Quebec
simon.wing@mcgill.ca
Office:
(514) 934-1934 ext. 76184
Expert In
Bio/Research
Ubiquitin-dependent proteolysis in skeletal muscle protein degradation
Skeletal muscle protein degradation plays a key role in metabolism by providing amino acid substrates for gluconeogenesis during starvation and in the pathological condition of diabetes. It is also activated in many d...
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Skeletal muscle protein degradation plays a key role in metabolism by providing amino acid substrates for gluconeogenesis during starvation and in the pathological condition of diabetes. It is also activated in many d...
Click to Expand >>
Bio/Research
Ubiquitin-dependent proteolysis in skeletal muscle protein degradation
Skeletal muscle protein degradation plays a key role in metabolism by providing amino acid substrates for gluconeogenesis during starvation and in the pathological condition of diabetes. It is also activated in many diseases (e.g. cancer, infection, stroke) as well as in normal aging and therefore plays a role in the muscle protein loss and atrophy that complicates these conditions. Our goal is to identify key enzymes that are responsible for the activation of protein degradation and could be pharmacologically inhibited to prevent or treat muscle wasting. A large body of evidence now indicates that the ubiquitin proteolytic pathway is activated in muscle atrophying in response to a wide variety of conditions and is probably responsible for the protein catabolism. We have recently identified a deubiquitinating enzyme that is induced in atrophying skeletal muscle and which when silenced activates myosin heavy chain expression. We are further characterizing the functions of this enzyme at both a cellular level and using mice bearing knockout of this gene.
Ubiquitin-dependent proteolysis during spermatogenesis
The loss of germ cell proteins is an important part of the cellular remodeling that takes place as spermatids mature to their elongated form. The mechanisms of degradation of these proteins remain unclear, but our studies have implicated the ubiquitin system in these degradative events. To date we have identified UBC4-testis, a member of the UBC4 family of ubiquitin conjugating enzymes which is induced during spermatogenesis. To evaluate its physiological function, we have inactivated the gene encoding the ubiquitin conjugating enzyme in mice and found that this causes a slight delay in testis maturation. To evaluate biochemical function, we have screened for ubiquitin protein ligases (enzymes which recognize substrates in the ubiquitin conjugating pathway) which interact with UBC4-testis. Interestingly, we have purified and identified a 500 kDa ligase (LASU1/Mule/ARFBP-1) which can polyubiquitinate histones which are degraded during spermatogenesis to permit chromatin condensation. We are using mouse knockout approaches to further explore the functions of this ligase as well as that of a deubiquitinating enzyme USP2 that is also induced during spermatogenesis.
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Skeletal muscle protein degradation plays a key role in metabolism by providing amino acid substrates for gluconeogenesis during starvation and in the pathological condition of diabetes. It is also activated in many diseases (e.g. cancer, infection, stroke) as well as in normal aging and therefore plays a role in the muscle protein loss and atrophy that complicates these conditions. Our goal is to identify key enzymes that are responsible for the activation of protein degradation and could be pharmacologically inhibited to prevent or treat muscle wasting. A large body of evidence now indicates that the ubiquitin proteolytic pathway is activated in muscle atrophying in response to a wide variety of conditions and is probably responsible for the protein catabolism. We have recently identified a deubiquitinating enzyme that is induced in atrophying skeletal muscle and which when silenced activates myosin heavy chain expression. We are further characterizing the functions of this enzyme at both a cellular level and using mice bearing knockout of this gene.
Ubiquitin-dependent proteolysis during spermatogenesis
The loss of germ cell proteins is an important part of the cellular remodeling that takes place as spermatids mature to their elongated form. The mechanisms of degradation of these proteins remain unclear, but our studies have implicated the ubiquitin system in these degradative events. To date we have identified UBC4-testis, a member of the UBC4 family of ubiquitin conjugating enzymes which is induced during spermatogenesis. To evaluate its physiological function, we have inactivated the gene encoding the ubiquitin conjugating enzyme in mice and found that this causes a slight delay in testis maturation. To evaluate biochemical function, we have screened for ubiquitin protein ligases (enzymes which recognize substrates in the ubiquitin conjugating pathway) which interact with UBC4-testis. Interestingly, we have purified and identified a 500 kDa ligase (LASU1/Mule/ARFBP-1) which can polyubiquitinate histones which are degraded during spermatogenesis to permit chromatin condensation. We are using mouse knockout approaches to further explore the functions of this ligase as well as that of a deubiquitinating enzyme USP2 that is also induced during spermatogenesis.
Click to Shrink <<