Disease relevance of NEFM

• Our data indicate that NF-M plays a key role in myelomonocytic differentiation, in signal transduction during macrophage activation and in the development of myelogenous leukemia [1].

High impact information on NEFM

• Remarkably, ectopic coexpression of Myb and NF-M proteins in erythroid cells or fibroblasts was sufficient to induce endogenous markers of myeloid differentiation, like the mim-1 and lysozyme genes [2].
• Here, we investigated the tissue-specific regulation of the mim-1 promoter and found that it not only contains binding sites for Myb but also for NF-M, a myeloid-specific transcription factor that probably corresponds to mammalian C/EBP beta [2].
• In situ hybridization revealed NF-M mRNA to be highly expressed in regions of the chick central nervous system, which contain multipolar and/or long-projection neurons [3].
• In addition, a truncated, dominant-negative form of NF-M inhibited cMGF expression in macrophages, indicating that NF-M is required for the normal activation of the gene [1].
• When multipotent hematopoietic progenitor cells were stimulated to differentiate, NF-M expression was induced at a very early stage, suggesting that the transcription factor plays a role in lineage commitment [1].

Biological context of NEFM

• The NF-M gene contains two introns which both are located within the highly conserved C-terminal region of the rod domain [4].
• To functionally analyze the NF-M promoter, constructs carrying 112, 222, and 1026 nucleotides of the 5' upstream region in front of a luciferase reporter gene were tested for their capability to direct luciferase expression after transient transfection into various cell lines [4].
• The NF-M transcription factor is related to C/EBP beta and plays a role in signal transduction, differentiation and leukemogenesis of avian myelomonocytic cells [1].
• NF-M stimulates the expression of the gene encoding cMGF, a myeloid cell-specific growth factor, creating an autocrine growth loop crucial to oncogene transformation of myeloid cells [1].
• Proteolytic cleavage and phosphopeptide mapping of 32P-labeled NF-M from control and treated cultures revealed that the phosphorylation of only one subset of phosphopeptides was affected by staurosporine, K252a, and LiCl [5].

Anatomical context of NEFM

• However, in spinal cords, there was only NF-M decreased, both of NF-H and NF-L kept unaffected [6].
• Large numbers of replicating neuroepithelial cells were found to express one of these proteins, NF-M, generations before the existence of any postmitotic neuroblasts (Days 1-2 1/2 of incubation) [7].
• Two-dimensional gels stained for protein further showed that the highly phosphorylated form of NF-M is transiently lost from embryonic optic nerve in E14, while the less phosphorylated form persists throughout the embryonic developmental stages [8].
• This transient NF-M expression was found in certain other cells of early embryos, including cardiac myoblasts [7].
• We have investigated ways of perturbing this process in intact cells and have found that phosphorylation of newly synthesized NF-M in cultured chick sensory neurons is inhibited by Li+ [9].

Associations of NEFM with chemical compounds

• The amino acid similarity between the Torpedo and rat NF-M approaches 90% in the amino-terminal "rod-like" domain and is significantly lower in the carboxy-terminal tail [10].
• Lithium chloride inhibits the phosphorylation of newly synthesized neurofilament protein, NF-M, in cultured chick sensory neurons [9].
• The rates of transport of labeled high (NF-H), medium (NF-M), and low (NF-L) molecular weight neurofilaments, and tubulin were faster in DFP-treated birds than in controls after 3 days [11].
• Western blot analysis showed increased expression of middle molecular weight neurofilament protein (NF-M), and decreased expression of high molecular weight (NF-H) and low molecular weight (NF-L) neurofilament proteins in the 2 M urea extracts of spinal cord particulate fraction [12].

Analytical, diagnostic and therapeutic context of NEFM

• An immunohistochemical survey was carried out on frozen sections of the early embryonic chick brain between 1 and 6 days of incubation, with antisera to the three neurofilament proteins (NF-L, NF-M, NF-H) [7].
• We also examined their effect on the post-translational mobility shift on SDS-PAGE that accompanies phosphorylation of newly synthesized NF-M [5].

References