Disease relevance of Tnpo1

• To understand this discrepancy, we compared a local tumor model with a metastatic one using MIP-1 alpha-transfected B16 F10 melanoma cells [1].
• HIV-1 protease, while the trigger of cataract formation, does not appear to be the protease responsible for cleavage of MIP or lens crystallins [2].
• In contrast, IL-1 (0.1 to 2.5 ng/ml), IFN-gamma (10 micrograms/ml), and IL-10 (2.5 to 10 ng/ml) were able to induce the significant production of MIP-1 by the granuloma fibroblasts [3].
• PURPOSE: Three different lens fiber cell intrinsic membrane proteins, MIP (Major Intrinsic Protein), MP19, and connexin50 (Cx50), have separately been implicated as causative candidates for congenital cataracts [4].
• CD8+ cell-secreted CC-chemokines, MIP-1alpha, and MIP-beta have recently been identified as factors which suppress HIV [5].

High impact information on Tnpo1

• These results suggest that TGF-beta may be capable of interfering with MIP-1 alpha's role as a stem cell inhibitor [6].
• Comparison of this MIP-1 beta cDNA with our previously cloned MIP-1 alpha sequence reveals that the MIP-1 peptides, members of a growing family of potential inflammatory mediators, are distinct but highly homologous (58.9% sequence identity) products of different genes [7].
• We recently reported the isolation of a novel monokine, macrophage inflammatory protein 1 (MIP-1), which causes local inflammatory responses in vivo, and induces superoxide production by neutrophils in vitro [7].
• Furthermore, F-peptide phosphorylation modulates the interaction of hnRNP A1 with transportin Trn1 [8].
• We demonstrate that PA is a potent activator of the inflammatory chemokines MIP (macrophage inflammatory protein)-1 alpha and MIP-1 beta (MIPs) mRNA expression in mouse macrophages in a dose- and time-dependent fashion and through a de novo protein synthesis-dependent process [9].

Biological context of Tnpo1

• By contrast to these apparent "macrophage activating" properties of MIP 1, the cytokine failed to trigger the macrophage oxidative burst, or to up-regulate the expression of Ia on the macrophage surface [10].
• These studies demonstrated constitutive expression of MCP-1 and differential up-regulation of MIP-1 on cytokine stimulation [3].
• The mRNA levels of gamma E- and/or gamma F-crystallin and MIP, markers of lens cell differentiation, are drastically reduced, while expression of ICSBP, a gamma IFN-inducible transcriptional factor, is induced in the alpha ACry-gamma IFN transgenic mouse eyes [11].
• METHODS: Study interaction of factors present in newborn mouse lens nuclear extracts with DNA fragments corresponding to mouse MIP gene 5' flanking sequence by electrophoresis mobility shift assay (EMSA) and DNase I footprinting [12].
• Cross reaction of antibodies against liver gap junction protein (26K) with lens fiber junction protein (MIP) suggests structural homology between these tissue specific gene products [13].

Anatomical context of Tnpo1

• MIP 1 treatment stimulated proliferation of mature tissue macrophages, and this effect was enhanced upon costimulations with either CSF-1 or granulocyte-macrophage-CSF [10].
• Interestingly, normal noninflammatory fibroblasts from uninfected mice showed no significant production of MIP-1 or MCP-1 in response to these cytokines [3].
• Thioglycollate-elicited peritoneal exudate macrophages incubated with native doublet MIP 1-secreted bioactive TNF and IL-6, as well as immunoreactive IL-1 alpha, and these effects were enhanced significantly when the cells were costimulated with IFN-gamma [10].
• The expression of FGF-3 in the lens rapidly induced epithelial cells throughout the lens to elongate and to express fiber cell-specific proteins including MIP and beta-crystallins [14].
• The role of MIP in lens fiber cell membrane transport [15].

Associations of Tnpo1 with chemical compounds

• We report here the resolution of MIP-1 into component peptides by SDS-hydroxylapatite chromatography, and compare the NH2-terminal sequences of the two peptides, now referred to as MIP-1 alpha and MIP-1 beta [7].
• Macrophage inflammatory protein 1 (MIP 1), initially purified from the conditioned medium of endotoxin-stimulated macrophages, is a low m.w. heparin-binding protein doublet comprising two peptides, MIP 1 alpha and MIP 1 beta [10].
• Pretreatment with LPS or addition of MIP-1 inhibited the in vitro migration of ESb-MP cells toward various chemokines [16].
• MIP has been hypothesized to be a gap junction protein, a membrane ion channel, a membrane water channel and a facilitator of glycerol transport and metabolism [15].
• Finally, PGE inhibits PMA and IFN-gamma-induced JE and MIP-1-related mRNA expression [17].

Other interactions of Tnpo1

• Macrophage inflammatory proteins MIP-1 and MIP-2 are involved in T cell-mediated neutrophil recruitment [18].
• Expression levels of IL-1beta, interferon-gamma inducible protein, macrophage inflammatory protein-1 (MIP-1) alpha, and MIP-1beta genes were 10- to 17-fold higher on day 5 after transplantation in C57BL/6 grafts on C57BL/6-presensitized recipients than in C57BL/6 grafts on unprimed recipients [19].
• This study examines the appearance of messenger RNA (mRNA) for cachectin/tumor necrosis factor (TNF), IL 1, and macrophage inflammatory proteins 1 and 2 (MIP-1 and MIP-2), as well as the mature peptides, in a model of wound healing using wound chambers [20].
• Tagged prothymosin alpha shared domains with mobile proteins such as Ran, transportin, and karyopherin beta, which also traverse the nuclear membrane, and co-localized with active RNA polymerase II [21].
• We have identified a novel CC chemokine family member, herein termed MIP-1 gamma in view of its similarity to existing members of the MIP-1 group [22].

Analytical, diagnostic and therapeutic context of Tnpo1

• Flow cytometry showed a significant increase in CD8(+) cells in lungs of mice with MIP-1 alpha-transfected tumors 3 days after injection [1].
• RESULTS: Examination of protein expression in c-Maf homozygous mutant mice revealed undetectable levels of CP49, CP115 and MIP protein. mRNA transcripts for these non-crystallin genes were observed at reduced levels in subsequent RT-PCR experiments [23].
• However, Western blot analysis revealed that iNOS protein production by TRN was 2-fold lower than that produced by B6/J2 [24].

References