Activation of nemo-like kinase in diamond blackfan anemia suppresses early erythropoiesis by preventing mitochondrial biogenesis.

ABSTRACT: Diamond Blackfan Anemia (DBA) is a rare macrocytic red blood cell aplasia that usually presents within the first year of life. The vast majority of patients carry a mutation in one of approximately 20 genes that results in ribosomal insufficiency with the most significant clinical manifestations being anemia and a predisposition to cancers. Nemo-like Kinase (NLK) is hyperactivated in the erythroid progenitors of DBA patients and inhibition of this kinase improves erythropoiesis, but how NLK contributes to the pathogenesis of the disease is unknown. Here we report that activated NLK suppresses the critical upregulation of mitochondrial biogenesis required in early erythropoiesis. During normal erythropoiesis, mTORC1 facilitates the translational upregulation of Transcription factor A, mitoc

SUBMITTER: Wilkes MC 

PROVIDER: S-EPMC11345392 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature