Prohibitin regulates mTOR pathway via interaction with FKBP8 / 医学前沿
Frontiers of Medicine
; (4): 448-459, 2021.
Artigo
em Inglês
| WPRIM (Pacífico Ocidental)
| ID: wpr-888730
Biblioteca responsável:
WPRO
ABSTRACT
The ability of tumor cells to sustain continuous proliferation is one of the major characteristics of cancer. The activation of oncogenes and the mutation or inactivation of tumor suppressor genes ensure the rapid proliferation of tumor cells. The PI3K-Akt-mTOR axis is one of the most frequently modified signaling pathways whose activation sustains cancer growth. Unsurprisingly, it is also one of the most commonly attempted targets for cancer therapy. FK506 binding protein 8 (FKBP8) is an intrinsic inhibitor of mTOR kinase that also exerts an anti-apoptotic function. We aimed to explain these contradictory aspects of FKBP8 in cancer by identifying a "switch" type regulator. We identified through immunoprecipitation-mass spectrometry-based proteomic analysis that the mitochondrial protein prohibitin 1 (PHB1) specifically interacts with FKBP8. Furthermore, the downregulation of PHB1 inhibited the proliferation of ovarian cancer cells and the mTOR signaling pathway, whereas the FKBP8 level in the mitochondria was substantially reduced. Moreover, concomitant with these changes, the interaction between FKBP8 and mTOR substantially increased in the absence of PHB1. Collectively, our finding highlights PHB1 as a potential regulator of FKBP8 because of its subcellular localization and mTOR regulating role.
Texto completo:
Disponível
Contexto em Saúde:
ODS3 - Meta 3.4 Reduzir as mortes prematuras devido doenças não transmissíveis
Problema de saúde:
Doenças do Sistema Endócrino
/
Neoplasia de Ovário
Base de dados:
WPRIM (Pacífico Ocidental)
Assunto principal:
Neoplasias Ovarianas
/
Proteínas Repressoras
/
Apoptose
/
Fosfatidilinositol 3-Quinases
/
Proteínas de Ligação a Tacrolimo
/
Proteômica
/
Linhagem Celular Tumoral
/
Proliferação de Células
/
Serina-Treonina Quinases TOR
Tipo de estudo:
Estudo prognóstico
Limite:
Feminino
/
Humanos
Idioma:
Inglês
Revista:
Frontiers of Medicine
Ano de publicação:
2021
Tipo de documento:
Artigo