Role of DOR/TP53INP2 in the control of muscle protein degradation = Papel de DOR/TP53INP2 en el control de la degradación de proteínas en el músculo esquelético
Protein homeostasis (proteostasis) results from the fine regulation of synthesis and degradation. The nuclear cofactor DOR/TP53INP2 was identified originally as a protein expressed in PML of nuclear bodies. However, in response to cellular stress, DOR/TP53INP2 exits the nucleus, localizes to early a...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2016 |
| País: | España |
| Institución: | CBUC, CESCA |
| Repositorio: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/402713 |
| Acceso en línea: | http://hdl.handle.net/10803/402713 |
| Access Level: | acceso abierto |
| Palabra clave: | Aparell locomotor Aparato locomotor Musculoskeletal system Proteïnes Proteínas Proteins Caquèxia Caquexia Cachexia Càncer Cáncer Cancer Ciències Experimentals i Matemàtiques 577 |
| Sumario: | Protein homeostasis (proteostasis) results from the fine regulation of synthesis and degradation. The nuclear cofactor DOR/TP53INP2 was identified originally as a protein expressed in PML of nuclear bodies. However, in response to cellular stress, DOR/TP53INP2 exits the nucleus, localizes to early autophagosomes and regulates autophagy. Recent data from our laboratory has demonstrated that DOR promotes muscle wasting by the activation of basal autophagy in skeletal muscle. Aim of this project is to analyze the role of DOR/TP53INP2 in combining the regulation of autophagy with other muscle homeostatic processes like the Ubiquitin- Proteasome System. Our results indicate that DOR is a negative regulator of the proteasome activity in C2C12 cells and skeletal muscle. Our data suggest that this upregulation of the proteasome activity in DOR-deficient cells is modulated by an induction of some subunits of the proteasome such as PSMD4 and PSMD11, subunits of the 19S regulatory particle involved in the recognition of Ub and proteasome assembly. Moreover, results suggest that DOR is also a negative regulator of protein synthesis. The comprehension of DOR function in regulating proteostasis will potentially identify new targets against muscle atrophy. Indeed, DOR expression is repressed in wasting conditions such as diabetes and cancer cachexia. |
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