RESUMEN

Molecular chaperones differ in their ability to stabilize nonnative polypeptides and to mediate protein folding, defining 'holding' and 'folding' systems. Here we show that the mammalian cytosolic and nuclear chaperone Hsc70 can act as both, as a 'holding' and a 'folding' system, depending on the chaperone cofactors which associate with Hsc70. In conjunction with the cofactor Hsp40, Hsc70 stabilizes heat-denatured firefly luciferase. The stabilizing activity turns into a folding activity in the additional presence of the Hsc70-interacting protein Hip. In contrast, the cofactor BAG-1 abrogates the 'holding' function of the Hsc70/Hsp40 system and blocks the action of Hip on Hsc70. Our study sheds light on the molecular mechanisms that determine the functional specificity of Hsc70 in the mammalian cell.

Asunto(s)

Adenosina Trifosfatasas/metabolismo , Proteínas Portadoras/metabolismo , Proteínas HSP70 de Choque Térmico , Chaperonas Moleculares/metabolismo , Animales , Proteínas de Unión al ADN , Proteínas del Choque Térmico HSC70 , Proteínas del Choque Térmico HSP40 , Proteínas de Choque Térmico/metabolismo , Calor , Humanos , Luciferasas/metabolismo , Desnaturalización Proteica , Pliegue de Proteína , Ratas , Especificidad por Sustrato , Factores de Transcripción