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PMID:9391090
| Citation |
Visvader, JE, Mao, X, Fujiwara, Y, Hahm, K and Orkin, SH (1997) The LIM-domain binding protein Ldb1 and its partner LMO2 act as negative regulators of erythroid differentiation. Proc. Natl. Acad. Sci. U.S.A. 94:13707-12 |
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| Abstract |
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. |
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| Keywords |
Adaptor Proteins, Signal Transducing; Animals; Basic Helix-Loop-Helix Transcription Factors; Cell Line; DNA, Complementary/genetics; DNA-Binding Proteins/chemistry; DNA-Binding Proteins/genetics; DNA-Binding Proteins/metabolism; DNA-Binding Proteins/physiology; Erythropoiesis/genetics; Erythropoiesis/physiology; Gene Expression Regulation, Developmental; In Situ Hybridization; LIM Domain Proteins; Macromolecular Substances; Metalloproteins/chemistry; Metalloproteins/genetics; Metalloproteins/physiology; Mice; Molecular Sequence Data; Multiprotein Complexes; Protein Binding; Proto-Oncogene Proteins; RNA, Messenger/genetics; RNA, Messenger/metabolism; Transcription Factors/metabolism |
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Significance
Annotations
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