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Targeting cellular senescence in cancer and aging: roles of p53 and its isoforms.
Beck, Jessica; Turnquist, Casmir; Horikawa, Izumi; Harris, Curtis.
Afiliação
  • Beck J; Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Turnquist C; Department of Comparative Pathobiology, Purdue University, West Lafayette, IN, USA.
  • Horikawa I; Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • Harris C; University of Oxford Medical School, John Radcliffe Hospital, Oxford, UK.
Carcinogenesis ; 41(8): 1017-1029, 2020 08 12.
Article em En | MEDLINE | ID: mdl-32619002
ABSTRACT
Cellular senescence and the associated secretory phenotype (SASP) promote disease in the aged population. Targeting senescent cells by means of removal, modulation of SASP or through cellular reprogramming represents a novel therapeutic avenue for treating cancer- and age-related diseases such as neurodegeneration, pulmonary fibrosis and renal disease. Cellular senescence is partly regulated by the TP53 gene, a critical tumor suppressor gene which encodes 12 or more p53 protein isoforms. This review marks a significant milestone of 40 years of Carcinogenesis publication history and p53 research and 15 years of p53 isoform research. The p53 isoforms are produced through initiation at alternative transcriptional and translational start sites and alternative mRNA splicing. These truncated p53 isoform proteins are endogenously expressed in normal human cells and maintain important functional roles, including modulation of full-length p53-mediated cellular senescence, apoptosis and DNA repair. In this review, we discuss the mechanisms and functions of cellular senescence and SASP in health and disease, the regulation of cellular senescence by p53 isoforms, and the therapeutic potential of targeting cellular senescence to treat cancer- and age-associated diseases.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Envelhecimento / Proteína Supressora de Tumor p53 / Senescência Celular / Carcinogênese / Neoplasias / Antineoplásicos Tipo de estudo: Etiology_studies Limite: Animals / Humans Idioma: En Revista: Carcinogenesis Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Envelhecimento / Proteína Supressora de Tumor p53 / Senescência Celular / Carcinogênese / Neoplasias / Antineoplásicos Tipo de estudo: Etiology_studies Limite: Animals / Humans Idioma: En Revista: Carcinogenesis Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Estados Unidos