Редактирование: TRAF4

TNF receptor-associated factor 4 (Cysteine-rich domain associated with RING and Traf domains protein 1) (Metastatic lymph node gene 62 protein) (MLN 62) (RING finger protein 83) [CART1] [MLN62] [RNF83]

==Publications==

{{medline-entry
|title=In vivo evidence that [[TRAF4]] is required for central nervous system myelin homeostasis.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/22363515
|abstract=Tumor Necrosis Factor Receptor-Associated Factors (TRAFs) are major signal transducers for the [[TNF]] and interleukin-1/Toll-like receptor superfamilies. However, [[TRAF4]] does not fit the paradigm of TRAF function in immune and inflammatory responses. Its physiological and molecular functions remain poorly understood. Behavorial analyses show that [[TRAF4]]-deficient mice ([[TRAF4]]-KO) exhibit altered locomotion coordination typical of ataxia. [[TRAF4]]-KO central nervous system (CNS) ultrastructure shows strong myelin perturbation including disorganized layers and disturbances in paranode organization. [[TRAF4]] was previously reported to be expressed by CNS neurons. Using primary cell culture, we now show that [[TRAF4]] is also expressed by oligodendrocytes, at all stages of their differentiation. Moreover, histology and electron microscopy show degeneration of a high number of Purkinje cells in [[TRAF4]]-KO mice, that was confirmed by increased expression of the Bax pro-apoptotic marker (immunofluorescence), TUNEL analysis, and caspase-3 activation and [[PARP1]] cleavage (western blotting). Consistent with this phenotype, [[MAG]] and NogoA, two myelin-induced neurite outgrowth inhibitors, and their neuron partners, NgR and p75NTR were overexpressed (Q-RT-PCR and western blotting). The strong increased phosphorylation of Rock2, a RhoA downstream target, indicated that the NgR/p75NTR/RhoA signaling pathway, known to induce actin cytoskeleton rearrangement that favors axon regeneration inhibition and neuron apoptosis, is activated in the absence of [[TRAF4]] (western blotting). Altogether, these results provide conclusive evidence for the pivotal contribution of [[TRAF4]] to myelination and to cerebellar homeostasis, and link the loss of [[TRAF4]] function to demyelinating or neurodegenerative diseases.
|mesh-terms=* Aging
* Animals
* Behavior, Animal
* Blotting, Western
* Body Weight
* Cells, Cultured
* Central Nervous System
* Fluorescent Antibody Technique
* GPI-Linked Proteins
* Homeostasis
* Locomotion
* Mice
* Mice, Knockout
* Myelin Proteins
* Myelin Sheath
* Myelin-Associated Glycoprotein
* Nerve Degeneration
* Neurites
* Neurons
* Nogo Proteins
* Oligodendroglia
* Purkinje Cells
* Receptors, Nerve Growth Factor
* Signal Transduction
* TNF Receptor-Associated Factor 4
* rhoA GTP-Binding Protein

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3281907
}}
{{medline-entry
|title=Age-dependent resistance to lethal alphavirus encephalitis in mice: analysis of gene expression in the central nervous system and identification of a novel interferon-inducible protective gene, mouse ISG12.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/12388728
|abstract=Several different mammalian neurotropic viruses produce an age-dependent encephalitis characterized by more severe disease in younger hosts. To elucidate potential factors that contribute to age-dependent resistance to lethal viral encephalitis, we compared central nervous system (CNS) gene expression in neonatal and weanling mice that were either mock infected or infected intracerebrally with a recombinant strain, dsTE12Q, of the prototype alphavirus Sindbis virus. In 1-day-old mice, infection with dsTE12Q resulted in rapidly fatal disease associated with high CNS viral titers and extensive CNS apoptosis, whereas in 4-week-old mice, dsTE12Q infection resulted in asymptomatic infection with lower CNS virus titers and undetectable CNS apoptosis. GeneChip expression comparisons of mock-infected neonatal and weanling mouse brains revealed developmental regulation of the mRNA expression of numerous genes, including some apoptosis regulatory genes, such as the proapoptotic molecules caspase-3 and [[TRAF4]], which are downregulated during development, and the neuroprotective chemokine, fractalkine, which is upregulated during postnatal development. In parallel with increased neurovirulence and increased viral replication, Sindbis virus infection in 1-day-old mice resulted in both a greater number of host inflammatory genes with altered expression and greater changes in levels of host inflammatory gene expression than infection in 4-week-old mice. Only one inflammatory response gene, an expressed sequence tag similar to human ISG12, increased by a greater magnitude in infected 4-week-old mouse brains than in infected 1-day-old mouse brains. Furthermore, we found that enforced neuronal ISG12 expression results in a significant delay in Sindbis virus-induced death in neonatal mice. Together, our data identify genes that are developmentally regulated in the CNS and genes that are differentially regulated in the brains of different aged mice in response to Sindbis virus infection.
|mesh-terms=* Aging
* Alphavirus Infections
* Animals
* Animals, Newborn
* Animals, Suckling
* Central Nervous System
* Encephalitis, Viral
* Gene Expression Profiling
* Gene Expression Regulation, Developmental
* Genetic Predisposition to Disease
* Membrane Proteins
* Mice
* Neurons
* Oligonucleotide Array Sequence Analysis
* Proteins
* Sindbis Virus
* Viral Proteins

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC136759
}}