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Preparation of Quality Inositol Pyrophosphates

Preparation of Quality Inositol Pyrophosphates

Published on: September 3, 2011

Regulación de un complejo inhibidor de la ciclina-CDK-CDK por inositol pirofosfatos

Young-Sam Lee¹, Sashidhar Mulugu, John D York

¹Howard Hughes Medical Institute, Faculty of Arts and Sciences Center for Systems Biology, Department of Molecular and Cellular Biology, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138, USA.

Science (New York, N.Y.)

|April 7, 2007

Resumen

El heptakisfosfato de mio-d-inositol (IP7) estimula la inhibición dependiente de Pho81 del complejo Pho80-Pho85 ciclina-CDK en la levadura. Este metabolito es crucial para la señalización de la homeostasis de los nutrientes durante la inanición de fosfato.

Área de la Ciencia:

El metabolismo celular es el metabolismo celular.
Biología molecular La biología molecular.
Genética de la levadura genética de la levadura.

Sus antecedentes:

El hambre de fosfato en la levadura en ciernes activa los genes de homeostasis de nutrientes.
Esta activación implica la inhibición del complejo Pho80-Pho85 ciclina-CDK por el inhibidor Pho81.
No se comprenden completamente los mecanismos reguladores precisos que vinculan la disponibilidad de fosfato con esta inhibición.

Objetivo del estudio:

Para identificar los componentes celulares que regulan la inhibición dependiente de Pho81 del complejo Pho80-Pho85.
Para aclarar el papel del heptakisfosfato de myo-d-inositol (IP7) en la señalización de la inanición por fosfato.

Principales métodos:

Aislamiento y caracterización de IP7 como una molécula reguladora.
Ensayos in vitro para probar el efecto de IP7 en la inhibición de Pho81-Pho85.
Medición de los niveles intracelulares de IP7 bajo condiciones de inanición de fosfato.
Análisis de mutantes de levadura con defectos en la producción de IP7.

Principales resultados:

Myo-d-inositol heptakisphosphate (IP7) fue identificado como un estimulador de la inhibición Pho81-dependiente Pho80-Pho85.
IP7 es esencial para la inhibición de Pho81-Pho85 in vitro.
Las concentraciones intracelulares de IP7 aumentan durante la inanición de fosfato.
Los mutantes de levadura que carecen de producción de IP7 no pueden inhibir Pho80-Pho85 en respuesta al hambre de fosfato.

Conclusiones:

Un metabolito, IP7, regula directamente un complejo ciclina-CDK.
Este hallazgo revela un nuevo mecanismo para la señalización mediada por metabolitos en la levadura.
Es probable que una compleja red metabólica integre las señales de disponibilidad de fosfato.

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