HSP70 Sequestration by Free α-globin Promotes Ineffective Erythropoiesis in β-thalassaemia

Arlet J, et al., 514(7521):242-6, Nature, 2014

Based on their in vitro studies, the authors demonstrate that the heat shock protein70 (HSP70) interacts with free α-globin chains during the maturation of human β-TM erythroblasts. As a result, HSP70 is secluded in the cytoplasm and GATA-1 transcription factor is no longer protected, causing an end-stage maturation arrest and apoptosis. Mutants of HSP70 and GATA-1 restore the maturation of β-TM erythroblasts and hence provide a platform for novel β-TM targeted therapeutics. An Octet RED instrument (equipped with SA sensors) was used to conduct protein interaction assays. HSP70 or AHSP proteins were biotinylated and captured onto SA sensors.

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