Video Experimental Relacionado
Updated: Mar 25, 2026
10:33
Efficient Purification and LC-MS/MS-based Assay Development for Ten-Eleven Translocation-2 5-Methylcytosine Dioxygenase
Published on: October 15, 2018
8.7K
El metabolismo desordenado de la metionina en los cánceres eliminados por MTAP/CDKN2A conduce a la dependencia del
Konstantinos J Mavrakis1, E Robert McDonald1, Michael R Schlabach1
1Novartis Institutes for Biomedical Research, Cambridge, MA 02139, USA.
Science (New York, N.Y.)
|February 26, 2016
Resumen
Los cánceres eliminados por MTAP acumulan MTA, inhibiendo el PRMT5. Esto crea una vulnerabilidad a la inhibición de PRMT5, lo que sugiere los inhibidores de PRMT5 como un tratamiento potencial para estos tumores.
Área de la Ciencia:
- En el campo de la oncología
- La bioquímica
- Genética del cáncer
Sus antecedentes:
- La 5-metiltioadenosina fosforilasa (MTAP) es crucial en la vía de rescate de la metionina.
- Las deleciones del gen MTAP son comunes en los cánceres humanos debido a la proximidad al gen supresor de tumores CDKN2A.
Objetivo del estudio:
- Investigar las consecuencias funcionales de la deleción de MTAP en el cáncer.
- Identificar estrategias terapéuticas dirigidas a los cánceres con deficiencia de MTAP.
Principales métodos:
- Examen de ARN de horquilla corta (shRNA) a gran escala en 390 modelos de líneas celulares de cáncer.
- Análisis de la acumulación de metabolito (metiltioadenosina - MTA) en las células eliminadas de MTAP.
- Evaluación de la actividad de la metiltransferasa PRMT5 y de la viabilidad celular.
Principales resultados:
- Las células cancerosas con deficiencia de MTAP presentan una disminución de la viabilidad tras el agotamiento de PRMT5.
- La MTA acumulada en las células eliminadas de MTAP inhibe la actividad de la metiltransferasa PRMT5.
- La deleción de MTAP sensibiliza a las células a la inhibición de PRMT5; la reintroducción de MTAP rescata esta dependencia.
Conclusiones:
- La acumulación de MTA en los cánceres eliminados por MTAP conduce a un estado hipomórfico de PRMT5, creando sensibilidad a la inhibición de PRMT5.
- Los inhibidores de PRMT5 representan una vía terapéutica prometedora para los tumores eliminados por MTAP/CDKN2A.
Videos de Conceptos Relacionados
03:03mTOR Signaling and Cancer Progression
5.0K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
5.0K
03:03mTOR Signaling and Cancer Progression
1.6K
1.6K
02:23Abnormal Proliferation
5.4K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.4K
01:22PI3K/mTOR/AKT Signaling Pathway
6.2K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
6.2K
01:46Electron Transport Chain: Complex I and II
19.5K
The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
ROS generation is regulated and maintained at moderate levels necessary...
19.5K
01:21Overview of Protein Metabolism
4.6K
Proteins are broken down into amino acids during digestion. Unlike fats and carbohydrates, which are stored for later use, proteins are not. Instead, amino acids are either used to produce ATP through oxidation or contribute to the creation of new proteins for the growth and repair of the body. Any surplus amino acids from the diet are converted into glucose or triglycerides rather than excreted.
Amino acids play various roles in the body once they are absorbed into cells. They are restructured...
Amino acids play various roles in the body once they are absorbed into cells. They are restructured...
4.6K