| Essential role of Bag-1 in differentiation and survival of hematopoietic and neuronal cells | |||||||||||
Abstract | |||||||||||
| By targeted gene disruption in mice, we show that Bag-1, a co-chaperone for Hsp70 which interacts with C-Raf, B-Raf, Akt, Bcl-2, steroid hormone receptors and other proteins, plays an essential role in survival of differentiating neurons and hematopoietic cells. Bag-1−/− mice exhibit massive apoptosis in the fetal liver and developing nervous system. Lack of Bag-1 does not disturb the primary function of Akt or Raf as the phosphorylation of the forkhead transcription factor FKHR and activation of Erk-1/2 are not affected. However, the defect correlates with the disturbance of a tripartite complex formed by Akt, B-Raf and Bag-1, with absence of Bad phosphorylation at Ser136. Furthermore, we observe reduced expression of members of the IAP family. Our data reveal that Bag-1 is an important physiological mediator of extracellular survival signals linked to the cellular mechanisms that prevent apoptosis in hematopoietic and neuronal progenitor cells. | |||||||||||
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