The LIM-domain binding protein Ldb1 and its partner LMO2 act as negative regulators of erythroid differentiation

AUTOR(ES)

Visvader, Jane E.

FONTE

The National Academy of Sciences of the USA

RESUMO

The nuclear LIM domain protein LMO2, a T cell oncoprotein, is essential for embryonic erythropoiesis. LIM-only proteins are presumed to act primarily through protein-protein interactions. We, and others, have identified a widely expressed protein, Ldb1, whose C-terminal 76-residues are sufficient to mediate interaction with LMO2. In murine erythroleukemia cells, the endogenous Lbd1 and LMO2 proteins exist in a stable complex, whose binding affinity appears greater than that between LMO2 and the bHLH transcription factor SCL. However, Ldb1, LMO2, and SCL/E12 can assemble as a multiprotein complex on a consensus SCL binding site. Like LMO2, the Ldb1 gene is expressed in fetal liver and erythroid cell lines. Forced expression of Ldb1 in G1ER proerythroblast cells inhibited cellular maturation, a finding compatible with the decrease in Ldb1 gene expression that normally occurs during erythroid differentiation. Overexpression of the LMO2 gene also inhibited erythroid differentiation. Our studies demonstrate a function for Ldb1 in hemopoietic cells and suggest that one role of the Ldb1/LMO2 complex is to maintain erythroid precursors in an immature state.

Documentos Relacionados

• Structural basis for the recognition of ldb1 by the N-terminal LIM domains of LMO2 and LMO4
• Identification of a TAL1 Target Gene Reveals a Positive Role for the LIM Domain-Binding Protein Ldb1 in Erythroid Gene Expression and Differentiation
• Ssdp proteins interact with the LIM-domain-binding protein Ldb1 to regulate development
• The T cell leukemia LIM protein Lmo2 is necessary for adult mouse hematopoiesis
• Tandem LIM domains provide synergistic binding in the LMO4:Ldb1 complex