Insights into the role and regulation of TCTP in skeletal muscle.
The translationally controlled tumor protein (TCTP) is upregulated in a range of cancer cell types, in part, by the activation of the mechanistic target of rapamycin (mTOR). Recently, TCTP has also been proposed to act as an indirect activator of mTOR. While it is known that mTOR plays a major role in the regulation of skeletal muscle mass, very little is known about the role and regulation of TCTP in this post-mitotic tissue. This study shows that muscle TCTP and mTOR signaling are upregulated in a range of mouse models (mdx mouse, mechanical load-induced hypertrophy, and denervation- and immobilization-induced atrophy). Furthermore, the increase in TCTP observed in the hypertrophic and atrophic conditions occurred, in part, via a rapamycin-sensitive mTOR-dependent mechanism. However, the overexpression of TCTP was not sufficient to activate mTOR signaling (or increase protein synthesis) and is thus unlikely to take part in a recently proposed positive feedback loop with mTOR. Nonetheless, TCTP overexpression was sufficient to induce muscle fiber hypertrophy. Finally, TCTP overexpression inhibited the promoter activity of the muscle-specific ubiquitin proteasome E3-ligase, MuRF1, suggesting that TCTP may play a role in inhibiting protein degradation. These findings provide novel data on the role and regulation of TCTP in skeletal muscle in vivo.
Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, 53706, USA.|Centre for Chronic Disease Prevention and Management, College of Health and Biomedicine, Victoria University, Melbourne, Victoria, 8001, Australia.|Institute for Sport, Exercise and Active Living (ISEAL), Victoria University, Melbourne, Victoria, 8001, Australia.
Craig A
CA
Goodman
Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, 53706, USA.
Allison M
AM
Coenen
Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, 53706, USA.
John W
JW
Frey
Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, 53706, USA.
Jae-Sung
JS
You
Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria, 3086, Australia.
Robert G
RG
Barker
Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria, 3086, Australia.
Barnaby P
BP
Frankish
Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria, 3086, Australia.
Robyn M
RM
Murphy
Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin, 53706, USA.
Troy A
TA
Hornberger
D000818:Animals; D001284:Atrophy / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D004195:Disease Models, Animal; D018274:Electroporation; D006984:Hypertrophy / Q000378:metabolism / Q000473:pathology; D007103:Immobilization; D007150:Immunohistochemistry; D051379:Mice; D018101:Mice, Inbred mdx; D009121:Muscle Denervation; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D000090324:Tumor Protein, Translationally-Controlled 1
D014408:Biomarkers, Tumor; C000715648:Tpt1 protein, mouse; D000090324:Tumor Protein, Translationally-Controlled 1
Duchenne muscular dystrophy; cancer; muscle atrophy; muscle hypertrophy; proteostasis