Cell stress promotes HSF-1-dependent nucleolar accumulation of FKBP51

GALLO LI, PIWIEN PILIPUK G, GALIGNIANA MD

SEEON, ALEMANIA

Congreso; 4th International Conference on the Hsp90 Chaperone Machinery; 2008

Cells have developed a number of processes to increase survival and adaptation to stress via heat-shock proteins (hsps). The expression of hsps is regulated by transcription factors belonging to the HSF family, HSF-1 being the best characterized member. FKBP51 is an hsp90-binding immunophilin (IMM) that shows properties of hsp. So far, the biological function of this IMM is poorly understood. Here we report that FKBP51, which is located in mitochondria, rapidly translocates to the nucleus upon the onset of the cell stress response. The IMM rapidly cycles-back to mitochondria when the stimulus is suppressed. Hsp70, a chaperone able to interact with TPR proteins such as FKBP51, parallels the properties of the IMM. In the nucleus, FKBP51 is shown in the nucleoplasm and also concentrates in nuclear speckles and nucleoli. Confocal microscopy imaging shows that nucleolar FKBP51 co-localizes with nucleophosmin and nucleolin, indicating that the IMM is recruited to the fibrillar center and the dense fibrillar component of the nucleolus. Because the physiological role of HSF-1 during the stress response implies its relocalization into nuclear stress granules and nucleoli, we also studied the nucleo-mitochondrial shuttling of FKBP51 in HSF-1-/- cells and found that FKBP51 remains in mitochondria. The overexpression of HSF-1 translocates FKBP51 to nuclear stress granules and nucleoli in the absence of stimuli, whereas co-expression of HSF-1 and FKBP51 favors the accumulation of both factors in nuclear granules. This suggests a functional association of both proteins in the nucleus. While the onset of stress arrests RNA synthesis, FKBP51 overexpression enhances BrUTP signal in nucleoli, suggesting rRNA accumulation. Taken together, these results indicate that FKBP51 participates in the nucleolar segregation of rRNAs and other components in nucleolar caps during the arrest generated by cellular stress, which stands for a novel and relevant biological function for FKBP51.