<b>OBJECTIVEb>The tripartite motif (TRIM) proteins are a family of more than 70 human members, however only a few of them have been well studied. It has been shown that TRIM proteins are involved in various cellular processes such as cell proliferation, differentiation, apoptosis and antiviral defense. The functions of TRIM38 are largely unknown. In this study we explore the effect of TRIM38 on NF-kappaB signaling pathway.

<b>METHODSb>293T cells were transfected with NF-kappaB-Luc and plasmids expressing TRIM38 and its mutants fused to Flag. 24 h after transfection, cells were harvested and luciferase activities were measured. Data are representative of three independent experiments with triplicate samples. The expression of proteins was analyzed by Western Blot.

<b>RESULTSb>TRIM38 could activate NF-kappaB signaling pathway. The mutants of TRIM38 affected the function of TRIM38. Only the mutant of SPRY domain deletion had no obviously influence of the function of TRIM38.

<b>CONCLUSIONb>Our study reveals that NF-kappaB is activated in response to TRIM38.

Colon cancer is the 3rd common malignancy and 4th common cause of cancer death in Korea. Recent studies have shown that abnormal inflammatory response plays a critical role in colon carcinogenesis. A striking example of connection between inflammation and cancer is NF-kappaB, in which key regulator of inflammation and immune response is associated with target for colon cancer treatment. Constitutive NF-kappaB expression in colon cancer is 40-80% in vivo as well as in vitro, and the inactivation of IKKbeta subunit can reduce tumor multiplicity. The possible mechanisms by which NF-kappaB can contribute to colon carcinogenesis include the activator of antiapoptotic gene expression, enhanced cell survival and proliferation, regulation of angiogenesis and promotion of metastasis of cancer cells. Recent insights into the role of NF-kappaB involved in colon cancer development as well as their relevance as therapeutic targets are herein discussed.
Colonic Neoplasms/*etiology/metabolism ; Humans ; I-kappa B Kinase/metabolism/physiology ; Inflammation ; NF-kappa B/metabolism/*physiology

NF-kappaB family is a kind of nuclear factors in B lymphocyte that can bind to the immunoglobulin kappa-chain enhancer and enhance transcriptional activity. NF-kappaB/Rel proteins, as a dimeric transcription factor, control the expression of genes that regulate a broad range of biological processes through canonical and non-canonical pathways. In the central nervous system, NF-kappaB controls inflammatory reactions and the apoptotic cell death following nerve injury. It also contributes to the infarction and cell death in stroke models and patients. However, NF-kappaB is essential for neurosurvival as well. NF-kappaB activation is a part of recovery process that may protect neurons against oxidative-stresses or brain ischemia-induced apoptosis and neurodegeneration. Inhibition of NF-kappaB may reduce its neuroprotection activity. Hence the dual opposite effects of NF-kappaB on cells. The ultimate survival or death of neurons depends on which, where and when the NF-kappaB factors are activated.
Animals ; Central Nervous System ; injuries ; physiology ; Humans ; NF-kappa B ; metabolism ; Nerve Regeneration ; physiology

Nuclear factor-kappa B (NF-kappa B) plays an important role in controlling infection, immunity responses, cellar differentiation and apoptosis. It is of characteristics especially in neural system. NF-kappa B exist widely in neural cells and transfer from plasma into nucleolus through diversified activation passages. in addition, NF-kappa B is also a key factor in the development of the neural system, anti-apoptosis and modulating the activity of glia cells. It is of great significance in the forensic science.
Apoptosis ; Cell Nucleus/metabolism* ; Forensic Medicine/methods* ; Microglia/physiology* ; NF-kappa B/physiology* ; Neurons/metabolism*

NF-kappaB is a kind of important nuclear factors which are relative to lots of cellular activities such as activation of immunocyte, development of T and B lymphocyte, stress reaction, cell apoptosis and so on. NF-kappaB exists in almost all types of cytoplasm in the unreactive form of heterodimer or homodimer. Recent studies have shown that there is close relationship between NF-kappaB and pathogenesis of hematopoietic malignancies such as leukemia, lymphoma and multiple myeloma. In this review, the advances of studies on the role of NF-kappaB in hematopoietic malignancies were summarized, including subunits of NF-kappaB and its activity, activity of NF-kappaB and its effect on apoptosis, activity of NF-kappaB in AML cells and its mechanism, activity of NF-kappaB in ATL cells and its mechanism, activity of NF-kappaB in lymphoma and its mechanism, activity of NF-kappaB in multiple myeloma cells and its mechanism, application of NF-kappaB suppression in hematopoietic malignancies and so on.
Apoptosis ; physiology ; Hematologic Neoplasms ; etiology ; immunology ; pathology ; Humans ; NF-kappa B ; immunology ; metabolism

Poxviruses, a type of ds-DNA viruses which mainly target at the epithelial cell, are the pathogens of human and animals. During the revolution of poxviruses, the viruses encode multiple proteins that regulate the immune system to monitor the viral reproductive cycle in host cells. The nuclear kappa B (NF-kappaB) pathway is essential to signal transcription in the innate immune system. Therefore, poxviruses have adopted different strategies to elude immune detection and destruction regulated by NF-kappaB. Further research in this field would help us develop preventive and therapeutic preparation for pox. Given the renewed interest in poxvirus, we review the current understanding of how the various classes of poxviralimmunomodulatory proteins target and manipulate the NF-kappaB pathway.
Animals ; Host Specificity ; Humans ; NF-kappa B ; metabolism ; Poxviridae ; physiology ; Signal Transduction

In this study, we aim to investigat the effect of microgravity on osteoblast differentiation in osteoblast-like cells (MC3T3-E1). In addition, we explored the response mechanism of nuclear factor-kappa B (NF-κB) signaling pathway to "zero- " in MC3T3-E1 cells under the simulated microgravity conditions. MC3T3-E1 were cultured in conventional (CON) and simulated microgravity (SMG), respectively. Then, the expression of the related osteoblastic genes and the specific molecules in NF-κB signaling pathway were measured. The results showed that the mRNA and protein levels of alkaline phosphatase (ALP), osteocalcin (OCN) and type Ⅰ collagen (CoL-Ⅰ) were dramatically decreased under the simulated microgravity. Meanwhile, the NF-κB inhibitor α (IκB-α) protein level was decreased and the expressions of phosphorylation of IκB-α (p-IκB-α), p65 and phosphorylation of p65 (p-p65) were significantly up-regulated in SMG group. In addition, the IL-6 content in SMG group was increased compared to CON. These results indicated that simulated microgravity could activate the NF-κB pathway to regulate MC3T3-E1 cells differentiation.
3T3 Cells ; Animals ; Cell Differentiation ; Mice ; NF-kappa B ; physiology ; Osteoblasts ; Signal Transduction ; Weightlessness Simulation

NF-kappaB, a collective name of dimeric transcription factors, is composed of members of the Rel family proteins that recognize and bind a specific DNA sequence. It is normally sequestered in the cytoplasm of non-stimulated cells by associating with a family of inhibitor proteins called IkappaBs. Exposure of cells to a variety of extra-and intra-cellular stimuli leads to the rapid proteolytic degradation of IkappaBs, which frees NF-kappaBs allowing them to translocate to the nucleus where it regulates gene transcription. NF-kappaB is involved in a lot of physiological processes such as immunity, inflammation, cell proliferation, apoptosis and even tumorigenesis by regulating the transcription of a larger number of genes. This review introduces the various mechanisms of NF-kappaB activation including a recently reported alternative activation pathway mediated by lymphotoxin alpha/beta, B cell activating factor and CD40 ligand. The signal transduction pathway leading to NF-kappaB activation via IKK in response to proinflammatory factors like TNF-alpha and IL-1 is addressed in more detail concerning the regulation of IKK activity, mechanism of IkappaB degradation and regulation of transactivation activity of NF-kappaB on different levels. Considering the important role of NF-kappaB in cell proliferation and regulation of various genes participating in apoptosis, the involvement of NF-kappaB in tumorigenesis and drug screening is also discussed.
Animals ; Drug Evaluation, Preclinical ; Humans ; I-kappa B Proteins ; metabolism ; NF-kappa B ; antagonists & inhibitors ; metabolism ; physiology ; Neoplasms ; etiology ; Signal Transduction ; Transcription, Genetic ; physiology

To investigate the expression of the subunit p65 of NF-kappaB and inhibitor kappa B alpha (IkappaBalpha) in mouse uterus during peri-implantation, thereby investigating whether transient activation of nuclear factor-kappaB (NF-kappaB) takes place during embryo implantation in mice. Immunohistochemical technique was used to examine the expression and localization of p65 in endometrium or deciduas, and Western blot analysis was employed to detect the levels of IkappaBalpha protein in mouse endometrium or deciduas. P65 protein was detected in stromal cells, epithelial cells of endometrium as well as in myometrium. Staining was predominately seen in the cytoplasm of the cells. Staining intensity for p65 was stronger in the epithelial compartment than the stromal compartment and myometrium. Staining intensity increased slightly during pregnancy, and it reached a high level on pregnancy day 5 and day 8. In contrast to p65, the level of IkappaBalpha protein was lowest on pregnancy day 5 in all groups. Our results suggested that NF-kappaB may regulate embryo implantation by its transient activation in mice.
Decidua/metabolism ; Embryo Implantation/*physiology ; Endometrium/metabolism ; I-kappa B Proteins/*biosynthesis ; NF-kappa B/*biosynthesis ; Time Factors ; Uterus/*metabolism ; Uterus/physiology

The modeling of signal transduction pathways is a task of systems biology. However, such a task is very difficult because of the structure complexity, the strong nonlinearity of signaling pathways and the noised and incomplete measurements. The Levenberg-Marquardt algorithm (LM algorithm) is applied to estimate the unknown parameters of the signaling pathways. With this method, the identifiability of unknown parameters is appraised, and the sensitivity equations of original model are evaluated. Then we append the sensitivity equations to the original model in order to form the augmented model, and we apply the Levenberg-Marquardt algorithm to the augmented model in order to estimate parameters. TNFalpha mediated NF-kappaB signaling pathway is taken as an example to illustrate the effectiveness of this method, and the simulation results are given.
Algorithms ; Computer Simulation ; Humans ; Models, Theoretical ; NF-kappa B ; physiology ; Signal Transduction ; Systems Biology ; methods ; Tumor Necrosis Factor-alpha ; physiology