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Yap1 actúa aguas abajo de la α-catenina para controlar la proliferación epidérmica
Karin Schlegelmilch1, Morvarid Mohseni, Oktay Kirak
1Stem Cell Program, Children's Hospital, Boston, MA 02115, USA.
Cell
|March 8, 2011
Resumen
Yap1, un componente clave de la vía Hippo, controla la proliferación de células madre epidérmicas y el crecimiento de tejidos en la piel de los mamíferos. La alfa-catenina actúa como un regulador negativo, modulando la actividad de Yap1 y contribuyendo a los mecanismos de "control de multitudes".
Área de la Ciencia:
- Biología celular Biología celular.
- Biología del desarrollo Biología del desarrollo.
- Dermatología Dermatología dermatología.
Sus antecedentes:
- La proliferación de células madre específicas del tejido está estrictamente regulada para la determinación del tamaño del órgano durante el desarrollo y la regeneración.
- Los mecanismos moleculares que rigen este control, particularmente en la piel, no se comprenden completamente.
- La vía de señalización de Hippo y su efector Yap1 son reguladores conocidos de la proliferación celular y el tamaño del órgano en varios contextos.
Objetivo del estudio:
- Para investigar el papel de Yap1, el efector de transcripción de la vía Hippo, en la biología de la piel.
- Para dilucidar los mecanismos moleculares por los cuales Yap1 regula la proliferación de células madre epidérmicas y la expansión del tejido.
- Para identificar los reguladores aguas arriba de Yap1 en el contexto de la homeostasis de la piel.
Principales métodos:
- Se emplearon estudios de ganancia y pérdida de función para evaluar el papel de Yap1 en las células madre epidérmicas.
- Investigó la interacción de Yap1 con los factores de transcripción TEAD.
- Se analizó el papel regulador de la α-catenina en la actividad de Yap1, incluida su fosforilación e interacciones con la 14-3-3 y la PP2A fosfatasa.
Principales resultados:
- Yap1 fue identificado como un modulador crítico de la proliferación de células madre epidérmicas y la expansión del tejido cutáneo.
- Yap1 ejerce su función a través de la interacción con los factores de transcripción TEAD.
- Se descubrió que la α-catenina es un regulador negativo aguas arriba de Yap1, controlando su actividad y estado de fosforilación mediante la modulación de las interacciones con la 14-3-3 y la PP2A fosfatasa.
Conclusiones:
- Yap1 es un determinante clave de la capacidad proliferativa de las células madre epidérmicas en la piel de los mamíferos.
- Yap1 actúa como un efector importante en un circuito molecular que controla el tamaño del tejido, similar al "control de multitudes".
- La α-catenina juega un papel importante en la regulación de la actividad de Yap1, contribuyendo a la detección de la densidad celular y la supresión de tumores en la piel.
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