Summary of links between HSP70/GATA1 and p53 stabilization in DBA erythroid phenotype, depending on the RP gene mutation.⁸⁴  Two DBA phenotypes have been identified in vitro from primary erythroid cells derived from DBA patients, depending on the mutated RP gene. Patients carrying a mutation in the RPS19 gene exhibit decreased erythroid proliferation but normal erythroid differentiation and no apoptosis. In contrast, DBA patients who carry a mutation in an RP gene other than RPS19 exhibit a large decrease in erythroid proliferation, delayed erythroid differentiation, and a large increase in apoptosis.⁸⁵  In the case of haploinsufficiency of the RPS19, RPL5, or RPL11 gene, erythroblastopenia in DBA results at least in part from stabilization of p53 and activation of p53 targets (p21, Bax), which are responsible for activation of apoptosis and cell-cycle arrest in G₀/G1 phases.^85,92  HSP70 has been identified as the key protein responsible for the observed dual DBA phenotypes.⁸⁴  Normal levels of HSP70 expression are noted in patients carrying a mutation in the RPS19 gene, whereas a large decrease in HSP70 expression is seen in patients who carry a mutation in the RPL5, RPL11, or RPS24 gene and even in patients with no identified genotype. HSP70 has been shown to be proteasomally degraded after ubiquitinylation. Decreased expression of HSP70 leads to the cleavage of GATA1 by caspase-3, which also leads to p53 stabilization, induction of apoptosis, and delayed erythroid differentiation. Apoptosis, delayed erythroid differentiation, and cell-cycle arrest lead to the decreased erythroid proliferation and characteristic erythroblastopenia seen in DBA.