Video Experimental Relacionado

Updated: May 2, 2026

Detection of Protein Ubiquitination

Detection of Protein Ubiquitination

Published on: August 19, 2009

NEDD4-1 es una ligasa de ubiquitina proto-oncogénica para PTEN

Xinjiang Wang¹, Lloyd C Trotman, Theresa Koppie

¹Cell Biology Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 522, New York, NY 10021, USA.

|January 16, 2007

Resumen

El supresor del tumor PTEN.

Área de la Ciencia:

Oncología Oncología.
Biología Molecular Biología Molecular
La bioquímica es la bioquímica.

Sus antecedentes:

El supresor tumoral PTEN es crucial para los procesos celulares y con frecuencia se altera en los cánceres.
La expresión reducida de PTEN tiene un impacto significativo en la carcinogénesis.
El papel de PTEN en el cáncer requiere la comprensión de sus mecanismos reguladores.

Objetivo del estudio:

Para aclarar el mecanismo de regulación de los niveles de proteínas PTEN.
Para identificar la ubiquitina ligasa responsable de la degradación del PTEN.
Investigar el papel de NEDD4-1 en la regulación de PTEN y el cáncer.

Principales métodos:

Pruebas de degradación proteasomales mediadas por ubiquitina.
Purificación e identificación de la ubiquitina ligasa de PTEN.
Pruebas de transformación celular.
Análisis de la expresión de NEDD4-1 en modelos de cáncer y muestras humanas.
Ensayos de inhibición del crecimiento tumoral xenotransplantado.

Principales resultados:

Los niveles de PTEN están regulados por la degradación proteasomal mediada por ubiquitina.
NEDD4-1 fue identificado como la ubiquitina ligasa para PTEN.
NEDD4-1 cataliza la poliubiquitinación de PTEN, reduciendo la estabilidad de PTEN.
La sobreexpresión de NEDD4-1 promovió la transformación celular.
La alta expresión de NEDD4-1 se correlacionó con bajos niveles de PTEN en cánceres con PTEN normal.
La eliminación de NEDD4-1 inhibió el crecimiento tumoral dependiendo de PTEN.

Conclusiones:

NEDD4-1 regula negativamente la estabilidad de PTEN a través de la ubiquitinación.
La regulación al alza aberrante de NEDD4-1 puede suprimir el PTEN en el cáncer.
NEDD4-1 actúa como un proto-oncogén al dirigirse a PTEN.
NEDD4-1 representa un objetivo terapéutico potencial en cánceres con bajo PTEN.

Más Videos Relacionados

Fluorescence-based Monitoring of PAD4 Activity via a Pro-fluorescence Substrate Analog

Fluorescence-based Monitoring of PAD4 Activity via a Pro-fluorescence Substrate Analog

Published on: November 5, 2014

Measuring Enzymatic Activity of Neurodevelopmental Disorder-Associated Deubiquitylating Enzymes via an In Vitro Ubiquitin Chain Cleavage Assay

Measuring Enzymatic Activity of Neurodevelopmental Disorder-Associated Deubiquitylating Enzymes via an In Vitro Ubiquitin Chain Cleavage Assay

Published on: September 27, 2024

Videos de Conceptos Relacionados

Covalently Linked Protein Regulators

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....

Nonsense-mediated mRNA Decay

Nonsense-mediated mRNA Decay

The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...

Canonical Wnt Signaling Pathway

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...

Abnormal Proliferation

Abnormal Proliferation

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...

PI3K/mTOR/AKT Signaling Pathway

PI3K/mTOR/AKT Signaling Pathway

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...

Catenins

Catenins

Catenins are characterized by multiple binding domains and dynamic structures that allow them to function as linker proteins in cell junction complexes. All catenins, except α-catenin, contain a characteristic protein sequence called the armadillo repeat and are therefore also called armadillo proteins.
Catenins in Cell Junctions
Catenins bind to cell adhesion molecules such as cadherins and link them to different cytoskeletal proteins depending on the type of cell junction. At the...