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La fosforilación de Hsp70 dependiente de CDK controla la abundancia de ciclina G1 y la progresión del ciclo celular

Andrew W Truman¹, Kolbrun Kristjansdottir, Donald Wolfgeher

¹Ludwig Center for Metastasis Research, The University of Chicago, Chicago, IL 60637, USA.

|December 11, 2012

Resumen

La fosforilación de la proteína de choque térmico 70 (Hsp70) por las cinasas dependientes de la ciclina (CDKs) controla la estabilidad de la ciclina G1 y la progresión del ciclo celular. Este mecanismo, conservado en los seres humanos, regula el crecimiento mediante la modulación de la abundancia y la actividad de la ciclina.

Área de la Ciencia:

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

Sus antecedentes:

Las chaperonas Hsp70 son proteínas esenciales que regulan las funciones celulares.
Su actividad está modulada por la expresión, la isoforma y las cochaperonas.

Objetivo del estudio:

Para investigar un nuevo mecanismo de regulación de la función Hsp70.
Explorar el papel de la fosforilación de Hsp70 en el control del ciclo celular.

Principales métodos:

Análisis del sitio de fosforilación en la levadura en ciernes Ssa1.1.
Investigando las interacciones entre Ssa1, Ydj1 y Cln3.
Estudiar los efectos de CDK Pho85 y Cdk1 en la fosforilación de Ssa1 y la estabilidad de Cln3.
Examinando la fosforilación conservada en humanos Hsc70 y Ciclina D1.1.

Principales resultados:

La fosforilación de Ssa1 en T36 por las CDKs altera las interacciones entre la cochaperona y el cliente.
La fosforilación T36 desplaza a Ydj1, lo que permite a Ssa1 unirse y degradar la ciclina G1 Cln3.3.
Las CDKs estresantes y mitóticas (Pho85, Cdk1) regulan la estabilidad de Cln3 a través de la fosforilación de Ssa1.
La fosforilación dependiente de CDK del Hsc70 T38 humano afecta la estabilidad de la ciclina D1.

Conclusiones:

Hsp70 actúa como un transductor de señales en el control del crecimiento celular.
La fosforilación Hsp70 mediada por CDK regula la abundancia y la actividad de la ciclina G1.
Este mecanismo de fosforilación se conserva de la levadura al hombre.

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