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p62/SQSTM1 in liver diseases: the usual suspect with multifarious identities.
Tan, Chong Teik; Soh, Natalie Jun Hui; Chang, Hao-Chun; Yu, Victor C.
Afiliación
  • Tan CT; Department of Pharmacy, National University of Singapore, Singapore.
  • Soh NJH; Department of Pharmacy, National University of Singapore, Singapore.
  • Chang HC; Department of Pharmacy, National University of Singapore, Singapore.
  • Yu VC; Department of Pharmacy, National University of Singapore, Singapore.
FEBS J ; 290(4): 892-912, 2023 02.
Article en En | MEDLINE | ID: mdl-34882306
p62/Sequestosome-1 (SQSTM1) is a selective autophagy receptor that recruits and delivers intracellular substrates for bulk clearance through the autophagy lysosomal pathway. Interestingly, p62 also serves as a signaling scaffold to participate in the regulation of multiple physiological processes, including oxidative stress response, metabolism, inflammation, and programmed cell death. Perturbation of p62 activity has been frequently found to be associated with the pathogenesis of many liver diseases. p62 has been identified as a critical component of protein aggregates in the forms of Mallory-Denk bodies (MDBs) or intracellular hyaline bodies (IHBs), which are known to be frequently detected in biopsy samples from alcoholic steatohepatitis (ASH), non-alcoholic steatohepatitis (NASH), and hepatocellular carcinoma (HCC) patients. Importantly, abundance of these p62 inclusion bodies is increasingly recognized as a biomarker for NASH and HCC. Although the level of p62 bodies seems to predict the progression and prognosis of these liver diseases, understanding of the underlying mechanisms by which p62 regulates and contributes to the development and progression of these diseases remains incomplete. In this review, we will focus on the function and regulation of p62, and its pathophysiological roles in the liver, by critically reviewing the findings from preclinical models that recapitulate the pathogenesis and manifestation of these liver diseases in humans. In addition, we will also explore the suitability of p62 as a predictive biomarker and a potential therapeutic target for the treatment of liver diseases, including NASH and HCC, as well as recent development of small-molecule compounds for targeting the p62 signaling axis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Carcinoma Hepatocelular / Enfermedad del Hígado Graso no Alcohólico / Neoplasias Hepáticas Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: FEBS J Asunto de la revista: BIOQUIMICA Año: 2023 Tipo del documento: Article País de afiliación: Singapur Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Carcinoma Hepatocelular / Enfermedad del Hígado Graso no Alcohólico / Neoplasias Hepáticas Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: FEBS J Asunto de la revista: BIOQUIMICA Año: 2023 Tipo del documento: Article País de afiliación: Singapur Pais de publicación: Reino Unido