RESUMO
Este artículo especial desgrana los mecanismos y aspectos centrales relacionados con tres moléculas: la eritropoyetina, el factor inducible por hipoxia (HIF) y la proteína von Hippel-Lindau (pVHL) que han dado lugar tras múltiples investigaciones a galardonar con el Peremio Nobel de Fisiología y Medicina 2019 a los científicos William G. Kaelin, Gregg L. Semenza y Peter J. Ratcliffe. Se señalan los mecanismos moleculares que tiene lugar en situación de normoxia, hipoxia y pseudohipoxia. El artículo termina señalando las perspectivas farmacológicas que ha abierto la relación investigadora de estos científicos en el campo del cáncer y de muchas enfermedades degenerativas
This special article discusses the mechanisms and central aspects related to three molecules: erythropoietin, hypoxia-induced factor (HIF) and von Hippel-Lindau protein (pVHL) that have led after multiple investigations to win the Nobel Prize in Physiology and Medicine 2019 to scientists William G. Kaelin, Gregg L. Semenza and Peter J. Ratcliffe. The molecular mechanisms taking place in a situation of normoxia, hypoxia and pseudohypoxia are indicated. The article ends by pointing out the pharmacological perspectives that the research of these scientists has opened in the field of cancer and many degenerative diseases
Assuntos
Humanos , Hipóxia/fisiopatologia , Neoplasias/genética , Fator 1 Induzível por Hipóxia/genética , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Publicações Periódicas como Assunto/estatística & dados numéricos , Pesquisa Biomédica/estatística & dados numéricos , Antineoplásicos/farmacologia , Doenças Neurodegenerativas/genética , Técnicas de Diagnóstico Molecular/métodos , Prêmio NobelRESUMO
Inactivation of the von Hippel-Lindau (VHL) tumour suppressor gene is responsible for the development of renal carcinomas, pheochromocytomas and tumours in other organs. The gene product (pVHL) is a central component in the oxygen-sensing pathway through its role in the regulation of the hypoxia-inducible factor (HIF). Loss of pVHL leads to activation of the HIF pathway in normoxia with the concomitant increase in tumour vascularisation due to the up-regulation of pro-angiogenic genes. However, although the role of pVHL in the regulation of HIF has proved to be important for tumour growth, other pVHL functions independent of HIF have been reported and help to explain why loss of VHL leads to renal cancer. Studies aimed to characterise other molecular pathways that shed light on its physiological roles as a gatekeeper gene in kidney and other organs will be very helpful for the development of novel anticancer therapies (AU)
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