[HTML][HTML] Protein phosphatase 2A catalytic subunit α (PP2Acα) maintains survival of committed erythroid cells in fetal liver erythropoiesis through the STAT5 pathway

W Chen, P Gu, X Jiang, HB Ruan, C Li… - The American journal of …, 2011 - Elsevier
W Chen, P Gu, X Jiang, HB Ruan, C Li, X Gao
The American journal of pathology, 2011Elsevier
Suppression of programmed cell death is critical for the final maturation of red blood cells
and depends largely on the anti-apoptotic effects of EpoR–STAT5–Bcl-x L signaling. As the
major eukaryotic serine/threonine phosphatase, protein phosphatase 2A (PP2A) regulates
multiple cellular processes, including apoptosis. However, whether PP2A plays a role in
preventing erythroid cells from undergoing apoptosis remains to be elucidated. We
conditionally inactivated the catalytic subunit α of PP2A (PP2Acα), which is the predominant …
Suppression of programmed cell death is critical for the final maturation of red blood cells and depends largely on the anti-apoptotic effects of EpoR–STAT5–Bcl-xL signaling. As the major eukaryotic serine/threonine phosphatase, protein phosphatase 2A (PP2A) regulates multiple cellular processes, including apoptosis. However, whether PP2A plays a role in preventing erythroid cells from undergoing apoptosis remains to be elucidated. We conditionally inactivated the catalytic subunit α of PP2A (PP2Acα), which is the predominant form of PP2Ac, during early embryonic hematopoiesis. Loss of PP2Acα in hematopoietic cells perturbed definitive erythropoiesis characterized by fetal liver atrophy, reduced Ter119+ cell number, abnormal expression patterns of molecular markers, less colony formation, and a reduction in definitive globin expression. Levels of erythropoiesis-promoting cytokines and initial seeding with hematopoietic progenitors remained unchanged in PP2AcαTKO fetal livers. We noted impaired expansion of the fetal erythroid compartment, which was associated with increased apoptosis of committed erythroid cells. Mechanistically, PP2Acα depletion markedly reduced Tyr694 phosphorylation of STAT5 and expression of Bcl-xL. Unexpectedly, PP2Acα-deficient embryos did not manifest any early embryonic vascular defects. Collectively, these data provide direct loss-of-function evidence demonstrating the importance of PP2Acα for the survival of committed erythroid cells during fetal liver erythropoiesis.
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