Regulation of Normal and Malignant Hematopoiesis by FBOX Ubiquitin E3 Ligases.

Hematopoiesis is responsible for numerous functions, ranging from oxygen transportation to host defense, to injury repair. This process of hematopoiesis is maintained throughout life by hematopoietic stem cells and requires a controlled balance between self-renewal, differentiation, and quiescence. Disrupting this balance can result in hematopoietic malignancies, including anemia, immune deficiency, leukemia, and lymphoma.

UBR5 HECT domain mutations identified in mantle cell lymphoma control maturation of B cells.

Coordination of a number of molecular mechanisms including transcription, alternative splicing, and class switch recombination are required to facilitate development, activation, and survival of B cells. Disruption of these pathways can result in malignant transformation. Recently, next-generation sequencing has identified a number of novel mutations in mantle cell lymphoma (MCL) patients including mutations in the ubiquitin E3 ligase UBR5.

Loss of FBXO9 Enhances Proteasome Activity and Promotes Aggressiveness in Acute Myeloid Leukemia.

The hematopoietic system is maintained throughout life by stem cells that are capable of differentiating into all hematopoietic lineages. An intimate balance between self-renewal, differentiation, and quiescence is required to maintain hematopoiesis and disruption of this balance can result in malignant transformation. , the substrate recognition component from the SCF E3 ubiquitin ligase family, is downregulated in patients with acute myeloid leukemia (AML) compared to healthy bone marrow, and this downregulation is particularly evident in patients with inv(16) AML.