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Una isomerasa peptidil-prolyl humana esencial para la regulación de la mitosis

K P Lu¹, S D Hanes, T Hunter

¹Molecular Biology and Virology Laboratory, The Salk Institute, La Jolla, California 92037, USA.

|April 11, 1996

Resumen

Pin1 humano, una isomerasa peptidi-prolyl cis/trans (PPIase), es esencial para la viabilidad celular y la regulación de la mitosis. Interactúa con la NIMA quinasa, lo que sugiere un papel conservado en el control del ciclo celular a través de los eucariotas.

Área de la Ciencia:

Biología celular Biología celular.
Biología Molecular Biología Molecular
La bioquímica es la bioquímica.

Sus antecedentes:

La NIMA quinasa es crucial para la progresión de la mitosis en el Aspergillus nidulans.
Las peptidil-prolyl cis/trans isomerasas (PPIases) están involucradas en el plegamiento y ensamblaje de las proteínas.
Anteriormente no se había identificado ninguna PPIasa como esencial para la viabilidad celular.

Objetivo del estudio:

Para identificar y caracterizar el homólogo humano de la levadura Ess1/Ptf1.1.
Investigar el papel de la PPIasa humana Pin1 en la regulación del ciclo celular.
Para dilucidar la interacción entre Pin1 y NIMA quinasa.

Principales métodos:

Estudios de interacción proteica para identificar los socios de unión de Pin1.
Ensayos funcionales en levadura y células HeLa para evaluar el papel de Pin1 en la mitosis.
Manipulación genética (depleción y sobreexpresión) de Pin1 en modelos celulares.

Principales resultados:

Se identificó Human Pin1, una PPIasa nuclear con un dominio WW.
Pin1 está estructuralmente y funcionalmente relacionado con la proteína esencial de levadura Ess1/Ptf1.
El agotamiento de Pin1/Ess1 causó la detención mitótica en las células de levadura y HeLa.
La sobreexpresión de Pin1 condujo a la detención de la fase G2 en las células HeLa.
La actividad de la PPIasa es esencial para la función de Ess1/Pin1.

Conclusiones:

Pin1 es una PPIasa esencial que regula la mitosis.
Pin1 probablemente atenúa la actividad de la cinasa NIMA a través de la interacción, controlando así la progresión del ciclo celular.
Pin1 representa un regulador conservado de la mitosis en los organismos eucariotas.

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