Video Experimental Relacionado
Updated: May 11, 2026
08:47
Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation
Published on: March 5, 2018
La caspasa-11 murina, una proteasa que interactúa con el ICE, es esencial para la activación del ICE
1Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Cell
|March 10, 1998
Resumen
La inactivación del gen Caspase-11 (casp-11) hace que los ratones sean resistentes al shock endotóxico. La caspasa-11 es esencial para la activación de la enzima de conversión de la interleucina-1 (ICE), lo que sugiere que es esencial.
Área de la Ciencia:
- Biología Molecular Biología Molecular
- Inmunología Inmunología.
- Investigación de la Muerte Celular.
Sus antecedentes:
- La familia de genes Ice/Ced-3 (caspase) juega un papel crítico en la muerte celular programada.
- La activación de la enzima de conversión de la interleucina-1 (ICE) es un evento clave en las respuestas inflamatorias como el shock séptico.
Objetivo del estudio:
- Investigar el papel de la caspasa-11 (casp-11) en las vías de muerte celular y las respuestas inflamatorias.
- Para determinar si casp-11 está involucrado en la activación de ICE.
Principales métodos:
- La orientación genética para crear ratones mutantes casp-11.
- Análisis de la resistencia al choque endotóxico en ratones mutantes.
- Evaluación de la producción de IL-1alfa e IL-1beta después de la estimulación de lipopolisacáridos.
- Los ensayos de apoptosis utilizan células de fibroblastos embrionarios mutantes casp-11.
- Co-inmunoprecipitación para estudiar las interacciones proteicas entre la pro-caspasa-11 y el pro-ICE.
Principales resultados:
- Los ratones mutantes Casp-11 muestran resistencia al choque endotóxico inducido por el lipopolisacárido.
- La producción de IL-1alfa e IL-1beta se bloquea en ratones mutantes casp-11 después de la estimulación de lipopolisacáridos.
- Las células mutantes Casp-11 son resistentes a la apoptosis inducida por la sobreexpresión del ICE.
- La pro-caspasa-11 interactúa físicamente con el pro-ICE en las células.
- La expresión de la caspasa-11 es crucial para la activación del ICE.
Conclusiones:
- Caspase-11 es un componente necesario del complejo ICE.
- La caspasa-11 es necesaria para la activación del ICE, jugando un papel vital en la señalización inflamatoria y la muerte celular.
Videos de Conceptos Relacionados
02:53CRISPR and crRNAs
Bacteria and archaea are susceptible to viral infections just like eukaryotes; therefore, they have developed a unique adaptive immune system to protect themselves. Clustered regularly interspaced short palindromic repeats and CRISPR-associated proteins (CRISPR-Cas) are present in more than 45% of known bacteria and 90% of known archaea.
The CRISPR-Cas system stores a copy of foreign DNA in the host genome and uses it to identify the foreign DNA upon reinfection. CRISPR-Cas has three different...
The CRISPR-Cas system stores a copy of foreign DNA in the host genome and uses it to identify the foreign DNA upon reinfection. CRISPR-Cas has three different...
01:31Regulation of the Unfolded Protein Response
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
01:24Caspases
Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.
01:17The Extrinsic Apoptotic Pathway
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
01:31The Intrinsic Apoptotic Pathway
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
01:20The JAK-STAT Signaling Pathway
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...