Disease relevance of LMO4

• We further identified the breast tumor suppressor BRCA1 as an LMO4-associated protein [1].
• Mutational analysis of the LMO4 gene, encoding a BRCA1-interacting protein, in breast carcinomas [2].
• Overexpression of LMO4 induces mammary hyperplasia, promotes cell invasion, and is a predictor of poor outcome in breast cancer [3].
• Here, we have identified estrogen receptor alpha (ERalpha) and its corepressor, metastasis tumor antigen 1 (MTA1), as two novel binding partners of LMO4 [4].
• Transcription regulator LMO4 interferes with neuritogenesis in human SH-SY5Y neuroblastoma cells [5].

Psychiatry related information on LMO4

• Differential expression of LMO4 protein in Alzheimer's disease [6].

High impact information on LMO4

• Down-regulation of LMO4 expression reduced proliferation of human breast cancer cells and increased differentiation of mouse mammary epithelial cells [3].
• Together, these findings suggest that deregulation of LMO4 in breast epithelium contributes directly to breast neoplasia by altering the rate of cellular proliferation and promoting cell invasion [3].
• The zinc finger protein LMO4 is overexpressed in a high proportion of breast carcinomas [3].
• Conversely, overexpression of LMO4 in noninvasive, immortalized human MCF10A cells promoted cell motility and invasion [3].
• To investigate cellular processes controlled by LMO4 and those that may be deregulated during oncogenesis, we used RNA interference [3].

Biological context of LMO4

• In functional assays, LMO4 was shown to repress BRCA1-mediated transcriptional activation in both yeast and mammalian cells [1].
• Since proto-oncogene deregulation can result from activating mutations in their coding or regulatory sequences, we explored whether the LMO4 gene undergoes somatic mutagenesis in breast cancer [2].
• To characterize the transcriptional capacity of HEN1 alone or together with LMO2 and LMO4, we performed reporter gene assays [7].
• Because LMO4 is up-regulated in human breast cancers, repression of ERalpha transactivation functions by LMO4 might contribute to the process of breast cancer progression by allowing the development of ERalpha-negative phenotypes, leading to increased aggressiveness of breast cancer cells [4].
• LMO4, a LIM domain-containing protein that belongs to a family of oncogenes, was identified in this assay [8].

Anatomical context of LMO4

• Expression of the LMO4 gene is developmentally regulated in the mammary gland and is up-regulated in primary breast cancers [1].
• Sequestration of Ldb1 by LMO2 in T-cells may prevent it binding other key partners, such as LMO4 [9].
• Mutation analysis of the coding and 3' untranslated regions of the LMO4 gene was performed on 82 primary breast and 22 tumor cell lines [2].
• Overexpression of HEN1 in hippocampal precursor cells resulted in neurite extension, which could be prevented by LMO4 [7].
• Consistent with this, silencing LMO4 expression in stable cell lines expressing the small interfering RNA of LMO4 decreased Stat3 activity [8].

Associations of LMO4 with chemical compounds

• Modulation of the interleukin-6 receptor subunit glycoprotein 130 complex and its signaling by LMO4 interaction [8].

Other interactions of LMO4

• Using LMO4 in a yeast two-hybrid screen, we have identified the cofactor CtIP as an LMO4-binding protein [1].
• LMO4 belongs to the LIM-only (LMO) group of transcriptional regulators that appear to function as molecular adaptors for protein-protein interactions [1].
• Consistent with this notion, LMO4 overexpression repressed ERalpha transactivation functions in an HDAC-dependent manner [4].
• Immunocytochemical analysis revealed a high level of LMO4 expression in the entorhinal cortex (EC) and in the CA1 hippocampal region of the control brains and a consistent decrease in the AD brains, correlated with the amount of neurofibrillary tangles (NFT) degenerating neurones and the severity of senile plaques deposition [6].
• We next applied the biotinylation tag to Ldb-1, a known partner of GATA-1, and characterized a number of novel interaction partners that are essential in erythroid development, in particular, Eto-2, Lmo4, and CdK9 [10].

Analytical, diagnostic and therapeutic context of LMO4

• Here, we show using protein engineering and enzyme-linked immunosorbent assay (ELISA) methodologies that LMO2 binds Ldb1 with a twofold lower affinity than does LMO4 [9].
• Overexpression of LMO4 enhanced the transcriptional activity and target gene expression of Stat 3 (signal transducers and activators of transcription 3) [8].
• Sequence analysis of the mouse Lmo4 gene shows that it spans about 18 kb and consists of at least six exons, including two alternatively spliced 5' exons [11].
• In situ hybridization to early mouse embryos of 8-14.5 days revealed a complex pattern of LMO4 expression spatially overlapping with NLI and LHX genes [12].

References