David Sala1, Antonio Zorzano. 1. aDevelopment, Aging and Regeneration Program (DARe), Sanford-Burnham Medical Research Institute, La Jolla, California, USA bInstitute for Research in Biomedicine (IRB Barcelona) cDepartament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Barcelona dCIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain.
Abstract
PURPOSE OF REVIEW: The main aim of this review is to summarize current knowledge of tumor protein p53-inducible nuclear protein 2 (TP53INP2) function and its role in skeletal muscle proteostasis. RECENT FINDINGS: Autophagy is directly involved in the regulation of skeletal muscle mass. Thus, excessive autophagy is associated with several diseases that cause muscle wasting, and it promotes the loss of muscle protein. Furthermore, compromised autophagy also leads to muscle atrophy. In this regard, TP53INP2 activates autophagy in skeletal muscle, thus causing a reduction in muscle mass. Moreover, TP53INP2 gain of function enhances muscle wasting in a highly catabolic context such as in streptozotocin-induced diabetes. However, TP53INP2 is naturally repressed in human insulin resistance and in murine models of diabetes. These observations suggest that TP53INP2 repression would reduce muscle atrophy under conditions that favor protein loss in skeletal muscle. SUMMARY: To date, there is no effective treatment for muscle wasting. Thus, the identification of new putative pharmacological targets to effectively treat this devastating condition is crucial. Given current knowledge about the role of TP53INP2 in skeletal muscle, this protein may be an optimal candidate to target for the prevention of muscle wasting.
PURPOSE OF REVIEW: The main aim of this review is to summarize current knowledge of tumor protein p53-inducible nuclear protein 2 (TP53INP2) function and its role in skeletal muscle proteostasis. RECENT FINDINGS: Autophagy is directly involved in the regulation of skeletal muscle mass. Thus, excessive autophagy is associated with several diseases that cause muscle wasting, and it promotes the loss of muscle protein. Furthermore, compromised autophagy also leads to muscle atrophy. In this regard, TP53INP2 activates autophagy in skeletal muscle, thus causing a reduction in muscle mass. Moreover, TP53INP2 gain of function enhances muscle wasting in a highly catabolic context such as in streptozotocin-induced diabetes. However, TP53INP2 is naturally repressed in humaninsulin resistance and in murine models of diabetes. These observations suggest that TP53INP2 repression would reduce muscle atrophy under conditions that favor protein loss in skeletal muscle. SUMMARY: To date, there is no effective treatment for muscle wasting. Thus, the identification of new putative pharmacological targets to effectively treat this devastating condition is crucial. Given current knowledge about the role of TP53INP2 in skeletal muscle, this protein may be an optimal candidate to target for the prevention of muscle wasting.
Authors: Eman A Toraih; Afaf T Ibrahiem; Manal S Fawzy; Mohammad H Hussein; Saeed Awad M Al-Qahtani; Aly A M Shaalan Journal: Oxid Med Cell Longev Date: 2017-09-20 Impact factor: 6.543