Disease relevance of Ldb1

• This DNA-linking activity required Ldb1 and increased with dimethyl sulfoxide-induced differentiation of murine erythroleukemia (MEL) cells [1].
• Transfection assay to the pituitary tumor derived LbetaT2 cells, and the Chinese hamster ovary cells demonstrated that CLIM2 acts as a corepressor of the porcine Lhx2 function [2].
• These mice demonstrated a significantly enhanced growth of liver cancer by means of tumor size and number, advocating for an essential role of Ldb1 in HCC development [3].

High impact information on Ldb1

• Using in vivo function and protein interaction assays, we found that Lhx3 binds directly to the LIM cofactor NLI to trigger V2 interneuron differentiation [4].
• Whereas the isolated PKR kinase domain (KD) was non-functional in vivo, expression of a glutathione S-transferase-KD fusion, or co-expression of KD fusions containing the heterodimerization domains of the Xlim-1 and Ldb1 proteins, restored PKR activity in yeast cells [5].
• This factor, referred to as LMO-4, is expressed in overlapping manner with Clim-2 in epidermis and in several other regions, including epithelial cells of the gastrointestinal, respiratory and genitourinary tracts, developing cartilage, pituitary gland, and discrete regions of the central and peripheral nervous system [6].
• 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 [7].
• These results suggest that Ssdp1 regulates the development of late head organizer tissues and body growth by functioning as an essential activator component of a Lim1 complex through interaction with Ldb1 [8].

Biological context of Ldb1

• These characteristics imply that Ldb1-Lmo4 interaction may function in the T cell developmental programme and that enforced expression of LMO1 or LMO2 by chromosomal translocations or transgenesis may displace Lmo4 from this complex and thereby influence T cell differentiation prior to T cell tumour occurrence [9].
• Expression of LIM-domain binding protein (ldb) genes during zebrafish embryogenesis [10].
• Here we show that targeted deletion of the Ldb1 gene in mice results in a pleiotropic phenotype [11].
• Ssdp1 regulates head morphogenesis of mouse embryos by activating the Lim1-Ldb1 complex [8].
• Ldb1 maps to the distal region of mouse chromosome 19 that is syntenic with human chromosome 10q [12].

Anatomical context of Ldb1

• In both the developing face and the limb buds we identify Fgf-8 as the likely candidate signalling molecule that regulates Clim-2 expression [13].
• We show that in common with both these Lim genes, Clim-2 expression is regulated by signals from overlying epithelium [13].
• In the mouse, embryonic expression of Clim-2 is particularly pronounced in facial ectomesenchyme and limb bud mesenchyme in association with Lim genes, Lhx-6 and Lmx-1 respectively [13].

Associations of Ldb1 with chemical compounds

• Cofactor CLIM2 promotes the repressive action of LIM homeodomain transcription factor Lhx2 in the expression of porcine pituitary glycoprotein hormone alpha subunit gene [2].

Physical interactions of Ldb1

• GIP was the first member of this family shown to interact with nuclear LIM interactor (NLI) [14].

Other interactions of Ldb1

• We have now identified a new member of the Lmo family, designated Lmo4, via its interaction with Ldb1 [9].
• Cell proliferation is globally reduced in Ssdp1(hsk/hsk) mutants, and approximately half also exhibit smaller body size, similar to the phenotype observed in Lim1 and Ldb1 mutants [8].

Analytical, diagnostic and therapeutic context of Ldb1

• The expression of CLIM2 gene in the anterior pituitary lobe was detected during the porcine fetal and postnatal period by RT-PCR analysis, suggesting that this protein is constitutively expressing and plays a basic role in the anterior pituitary [2].

References