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Sterol regulatory element-binding proteins, designated as SREBP-1 and -2, are synthesized as membrane-bound proteins. They are localized on the endoplasmic reticulum membrane and the nuclear envelope, and activated by a two-step proteolytic processing. The NH2-terminal processed forms are released in the cytosol only when the intracellular cholesterol level is low, and translocated to the nucleus, resulting in the stimulation of transcription of the target genes. The transcriptional regulation requires either Sp1 or NF-Y, which binds its specific DNA-binding site close to the SREBP-binding site. On the contrary, the transcription of the MTP (Microsomal Triglyceride transfer Protein) gene is down-regulated by SREBPs without any participation of either Sp1 or NF-Y.

Transcription factor, NF-IL6 recognizes the same nucleotide sequences as C/EBP, and it is predominantly expressed in macrophages. Tanaka et al. reported that NF-IL6 knockout mice are highly susceptible to Listeria monocytogenes and Salmonella typhimurium due to impairment of bacteria killing by activated macrophages. We have tried to see the susceptibility for Mycobacterium leprae infection with intraperitoneal(i.p.) or both hind foot pad (BHF) in the NF-IL6 knockout mice with wild control mice. Although we examined the cytokine genes expression and induction of such as IL-1 alpha, IL-6, IL-12, IL-18/IGIF, NO2. and TNF alpha in the peritoneal macrophages on 1 month after inoculation, also IL-2 and IL-10 by splenocytes on 1 and 8 months after infection. Following the inoculation of M. leprae with i.p. or BHF, the mice were sacrificed from 1 to 12 months after inoculation in order to confirm the multiplication and the dissemination of the infection. Many leprosy bacilli was found in the peritoneal macrophages of NF-IL6 knockout mice on 1 month after inoculation while that of the wild control mice was showing disappear. In the case of the intraperitoneal infection, NF-IL6 knockout mice shows predominantly multiplication of M. leprae on the abdemino-organs such as omentum and also scrotum with male. Although NF-IL6 knockout mice with BHF inoculation did not show any swelling at the site of inoculated foot, however the foot pad on 12 month after inoculation was processed for Fite-Faraco's stain and microscopy shows many leprosy bacilli in the intermuscular layer or around the blood vessels/sciatic nerve in the subcutaneous tissue and then the multiplication extended to the toes. Besides the induction of cytokines such as IL-1 alpha, TNF alpha and IL-12 production were observed stronger in culture supernatant of peritoneal macrophages of NF-IL6 knockout mice than that of the wild control mice. IL-2 production was also observed strong in culture supernatant in splenocytes of NF-IL6 knockout mice while that of IL-10 production never induced at anytime. This is doubtless the results of impairment of bacteria killing by macrophages via NF-IL6 gene dependent mechanism not to antigen specific immune system.

MDR1 promoter activity increases in response to various environmental stimuli, including anticancer drugs and in a manner that is dependent on the inverted CCAAT box. The binding activity of a nuclear factor MDR-NF1 that interacts with this promoter region was augmented when the nuclear extract was prepared from cells that had been treated with either UV or anticancer drugs. In an attempt to understand the molecular basis for the stress-dependent induction of MDR1 promoter activity, the cDNA for MDR-NF1 have been cloned. The amino acid sequence encoded by the cloned cDNA was identical to that of YB-1. The human Y-Box binding protein (YB-1) is a member of a DNA-binding protein family with a structurally and functionally conserved cold shock domain. YB-1 was found to be much higher in all cisplatin-resistant cell lines than that in the respective drug-sensitive parental counterparts. Two transfectants with a YB-1 antisense construct showed increased sensitivity to cisplatin, mitomycin C and UV irradiation, but not to vincristine, doxorubicin, camptothecin or etoposide. Thus, YB-1 may protect cells from the cytotoxic effects of agents that induce cross-linking of DNA, suggesting a novel function of this ancestor DNA binding protein. Regulatory mechanism of the YB-1 gene expression and the cellular functions of YB-1 are currently under investigation in relation to drug resistance.

NF-IL6 and NF-kappa B are nuclear proteins supposed to play an important role in the regulation of acute-phase protein synthesis and inflammatory response against infection and tissue injury as a host defence mechanism. In addition the promoter region of the interleukin-6 (IL-6) gene has a NF-kappa B binding motif as well as a NF-IL6 binding site. Considering of these facts, we come to investigate that there may be a synergistic effect between NF-IL6 and NF-kappa B in the regulation of IL-6 gene expression. In order to study it, some combinations of expression vectors NF-IL6 cDNA, NF-kappa B (p50/p65) cDNA and reporter plasmid K18-CAT which contains human IL-6 promoter linked to the chloramphenicol acetyltransferase (CAT) gene, were transfected into Jurkat cells and the CAT activities were examined. Co-transfection of NF-IL6 and NF-kappa B (p50/p65) cDNA revealed a dramatic increase of acetylated [14C] chloramphenicol, and its CAT activity reached to 40%. Then, co-transfection of NF-IL6 and NF-kappa B subunit p65 alone showed a high level of CAT activity, too. When 5' deletion mutant reporter plasmid K9-CAT lacking the NF-IL6 binding site was used, co-transfection of NF-IL6 and NF-kappa B (p50/p65) showed low level of CAT activity. These results indicate that there is a synergistic effect between NF-IL6 and NF-kappa B (p50/p65) in IL-6 gene regulation. Among two subunits of NF-kappa B (p50/p65), p65 seems to play an important role rather than p50 does in synergism between NF-IL6 and NF-kappa B. Besides, this synergistic function comes to work only when NF-IL6 binds to its binding site of IL-6 promoter region.