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Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

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Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
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The Ras Gene02:38

The Ras Gene

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The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a...
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The Retinoblastoma Gene01:20

The Retinoblastoma Gene

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Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
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Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

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Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR...
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Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

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Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
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Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal01:22

Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal

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Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
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Video Experimental Relacionado

Updated: May 5, 2026

A Combined 3D Tissue Engineered In Vitro/In Silico Lung Tumor Model for Predicting Drug Effectiveness in Specific Mutational Backgrounds
13:34

A Combined 3D Tissue Engineered In Vitro/In Silico Lung Tumor Model for Predicting Drug Effectiveness in Specific Mutational Backgrounds

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EGFR en el limbo.

Michael J Eck1, William C Hahn

  • 1Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA. eck@red.dfci.harvard.edu

Cell
|May 15, 2012
PubMed
Resumen
Este resumen es generado por máquina.

Las mutaciones oncogénicas en el receptor del factor de crecimiento epidérmico (EGFR) promueven el cáncer al estabilizar un estado de quinasa desordenado, lo que lleva a una activación aberrante. Esta investigación revela cómo las mutaciones del EGFR impulsan el cáncer a través de la inestabilidad estructural.

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Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation
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Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation
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Área de la Ciencia:

  • La bioquímica es la bioquímica.
  • Biología Molecular Biología Molecular
  • Investigación de Investigación del Cáncer.

Sus antecedentes:

  • La señalización del receptor del factor de crecimiento epidérmico (EGFR) es crucial para las funciones celulares normales.
  • La activación del EGFR generalmente requiere la unión de ligandos, lo que lleva a la dimerización del receptor.
  • La señalización aberrante del EGFR, impulsada por mutaciones, es un sello distintivo de muchos cánceres.

Objetivo del estudio:

  • Investigar las bases estructurales de la activación oncogénica del EGFR.
  • Para entender cómo las mutaciones en el EGFR superan los mecanismos reguladores normales.

Principales métodos:

  • Análisis estructural del dominio de la quinasa del EGFR.
  • Análisis bioquímicos para evaluar los estados de dimerización y activación.

Principales resultados:

  • La quinasa EGFR existe en un estado parcialmente desordenado.
  • Las mutaciones oncogénicas estabilizan este estado desordenado, promoviendo la dimerización.
  • La estabilización del estado desordenado conduce a la activación del EGFR independiente del ligando.

Conclusiones:

  • Un estado parcialmente desordenado de la EGFR quinasa es intrínsecamente inestable.
  • Las mutaciones oncogénicas contrarrestan esta inestabilidad, impulsando una señalización aberrante del EGFR.
  • Dirigirse a esta inestabilidad estructural podría ofrecer nuevas estrategias terapéuticas para los cánceres con mutantes del EGFR.