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Family Transcription Factor (family + transcription_factor)
Selected AbstractsThe T-cell receptor repertoire of regulatory T cellsIMMUNOLOGY, Issue 4 2008Rafal Pacholczyk Summary The CD4+ CD25+ regulatory population of T cells (Treg cells), which expresses the forkhead family transcription factor (Foxp3), is the key component of the peripheral tolerance mechanism that protects us from a variety of autoimmune diseases. Experimental evidence shows that Treg cells recognize a wide range of antigenic specificities with increased reactivity to self antigens, although the affinity of these interactions remains to be further defined. The Treg repertoire is highly diverse with a distinct set of T-cell receptors (TCRs), and yet is overlapping to some extent with the repertoire of conventional T cells (Tconv cells). The majority of Treg cells are generated in the thymus. However, the role of the TCR specificity in directing thymic precursors to become Treg or Tconv cells remains unclear. On the one hand, the higher self reactivity of Treg cells and utilization of different TCRs in Treg and Tconv repertoires suggest that in TCR interactions an initial decision is made about the ,suitability' of a developing thymocyte to become a Treg cell. On the other hand, as Treg cells can recognize a wide range of foreign antigens, have a diverse TCR repertoire, and show some degree of overlap with Tconv cells, the signals through the TCR may be complementary to the TCR-independent process that generates precursors of Treg cells. In this review, we discuss how different features of the Treg repertoire influence our understanding of Treg specificities and the role of self reactivity in the generation of this population. [source] Mechanism of low CO2 -induced activation of the cmp bicarbonate transporter operon by a LysR family protein in the cyanobacterium Synechococcus elongatus strain PCC 7942MOLECULAR MICROBIOLOGY, Issue 1 2008Takashi Nishimura Summary The cmp operon of the cyanobacterium Synechococcus elongatus strain PCC 7942, encoding the subunits of the ABC-type bicarbonate transporter, is activated under CO2 -limited growth conditions in a manner dependent on CmpR, a LysR family transcription factor of CbbR subfamily. The 0.7 kb long regulatory region of the operon carried a single promoter, which responded to CO2 limitation. Using the luxAB reporter system, three cis -acting elements involved in the low-CO2 activation of transcription, each consisting of a pair of LysR recognition signatures overlapping at their ends, were identified in the regulatory region. CmpR was shown to bind to the regulatory region, yielding several DNA,protein complexes in gel shift assays. Addition of ribulose-1,5-bisphosphate (> 1 mM) or 2-phosphoglycolate (> 10 ,M) enhanced the binding of CmpR in a concentration-dependent manner, promoting formation of large DNA,protein complexes. Given the involvement of O2 in adaptive responses of cyanobacteria to low-CO2 conditions, our results suggest that 2-phosphoglycolate, which is produced by oxygenation by ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) of ribulose-1,5-bisphosphate under CO2 -limited conditions, acts as the co-inducer in the activation of the cmp operon by CmpR. [source] Revealing frequent alternative polyadenylation and widespread low-level transcription read-through of novel plant transcription terminatorsPLANT BIOTECHNOLOGY JOURNAL, Issue 7 2010Aiqiu Xing Summary Plant genetic engineering can create transgenic crops with improved characteristics by introducing trait genes through transformation. Appropriate regulatory elements such as promoters and terminators have to be present in certain configurations for the transgenes to be properly expressed. Five terminators native to soybean genes-encoding a MYB family transcription factor (MYB2), a Kunitz trypsin inhibitor (KTI1), a plasma membrane intrinsic protein (PIP1), a translation elongation factor (EF1A2) and a metallothionein protein (MTH1) were cloned and tested for their ability to enable transgene expression, mRNA polyadenylation and transcription termination. The terminators are as good as a control terminator of the potato proteinase inhibitor II gene (PINII) in conferring proper transgene expression, leading to mRNAs with various polyadenylation sites and terminating mRNA transcripts. RNA transcription read-through was detected in all transgenic plants and was quantified by qRT-PCR to be <1% at positions ,1 kb downstream of the 5, ends of different terminators. The detection of read-through RNA transcripts of the corresponding endogenous genes up to approximately 1 kb beyond the polyadenylation sites suggests that limited RNA transcription read-through is a normal phenomenon of gene expression. The study also provided more choices of terminators for plant genetic engineering when constructing DNA constructs containing multiple gene expression cassettes. [source] Identification and expression analysis of a MYB family transcription factor in the parasitic plant Orobanche ramosaANNALS OF APPLIED BIOLOGY, Issue 2 2007C.I. González-Verdejo Abstract MYB proteins are transcription factors (TFs) involved in the regulation of developmental processes in eukaryotes. A number of MYB genes have been identified from plants, but they have not been studied in parasitic plants. In this work, a member of the R2R3 MYB family of TFs was isolated from a complementary DNA library representing different developmental stages of the parasitic plant Orobanche ramosa. The pattern of expression of the gene was studied by in situ hybridisation. Alignment of the deduced Or-MYB1 protein with members of the MYB family showed the highest overall identity with MYB.Ph3 from petunia (Petunia hybrida), NtMYBAS1/S2 from tobacco (Nicotiana tabacum) and AtMYB101 from Arabidopsis thaliana. Amino acid sequence comparisons of DNA-binding domains showed that Or-MYB1 protein forms a closely related group with these proteins. Transcripts of Or-MYB1 were detected during all the developmental stages analysed, and in situ hybridisation showed that the expression was restricted to the parenchymatic cells proximal to the vascular vessels. These findings are consistent with a role of Or-MYB1 during early stages of development of O. ramosa, probably through the phenylpropanoid pathway. [source] Regulation of autophagy in human and murine cartilage: Hypoxia-inducible factor 2 suppresses chondrocyte autophagyARTHRITIS & RHEUMATISM, Issue 5 2009Jolene Bohensky Objective We have previously demonstrated that the transcription factor hypoxia-inducible factor 1 (HIF-1) promotes the onset of autophagy in chondrocytes. The overall goal of this study was to test the hypothesis that another HIF family transcription factor, HIF-2, modulates the induction of autophagy by chondrocytes. Methods Expression of HIF-1, HIF-2, and light chain 3 (LC3) in human and murine articular cartilage was visualized by immunohistochemistry. Suppression of HIF-2 was achieved using small interfering RNA technology. Assessments of autophagic flux and lysosomal activity, as well as ultrastructural analysis, were performed in chondrocytes in cell culture. Results HIF-2 was expressed abundantly by cells in human and murine articular cartilage and in the cartilage of mineralizing vertebrae from neonatal mice. Protein levels were reduced in articular cartilage from older mice, in end-plate cartilage from mice, and in chondrocytes from human osteoarthritic (OA) cartilage. HIF-2 was robustly expressed in the prehypertrophic cells of mouse growth cartilage. When HIF-2, was silenced, the generation of reactive oxygen species was found to be elevated, with a concomitant decrease in catalase and superoxide dismutase activity. Suppression of HIF-2 was associated with decreased Akt-1 and mammalian target of rapamycin activities, reduced Bcl-xL expression, and a robust autophagic response, even under nutrient-replete conditions. In these silenced chondrocytes, HIF-1 expression was elevated. Decreased HIF-2 expression was associated with autophagy in OA tissues and aging cartilage samples. The autophagic response of chondrocytes in HIF-2,,knockout mouse growth plate showed an elevated autophagic response throughout the plate. Conclusion Based on these observations, we conclude that HIF-2 is a potent regulator of autophagy in maturing chondrocytes. Our data suggest that this protein acts as a brake on the autophagy-accelerator function of HIF-1. [source] ESE-3, an Ets family transcription factor, is up-regulated in cellular senescenceCANCER SCIENCE, Issue 9 2007Makoto Fujikawa Normal cells irreversibly stop dividing after being exposed to a variety of stresses. This state, called cellular senescence, has recently been demonstrated to act as a tumor-suppressing mechanism in vivo. A common set of features are exhibited by senescent cells, but the molecular mechanism leading to the state is poorly understood. It has been shown that p38, a stress-induced mitogen-activated protein kinase (MAPK), plays a pivotal role in inducing cellular senescence in diverse settings. To better understand the senescence-inducing pathway, microarray analyses of normal human fibroblasts that ectopically activated p38 were performed. It was found that five genes encoding ESE-3, inhibin ,A, RGS5, SSAT and DIO2 were up-regulated in senescent cells induced by RasV12, H2O2 and telomere shortening, but not in quiescent or actively growing cells, suggesting that these genes serve as molecular markers for various types of cellular senescence. The ectopic expression of ESE-3 resulted in retarded growth, up-regulation of p16INK4a but not of p21, and increased levels of SA-,-gal activity. In contrast, RGS5, SSAT and the constitutive active form of the inhibin ,A receptor gene did not induce such senescence phenotypes when ectopically expressed. ESE-3 expression increased the activity of the p16INK4a promoter in a reporter assay, and recombinant ESE-3 protein bound to the Ets-binding sequences present in the promoter. These results suggest that ESE-3 plays a role in the induction of cellular senescence as a downstream molecule of p38. (Cancer Sci 2007; 98: 1468,1475) [source] Ultraviolet radiation stimulates expression of Snail family transcription factors in keratinocytesMOLECULAR CARCINOGENESIS, Issue 4 2007Laurie G. Hudson Abstract The related zinc finger transcription factors Slug and Snail modulate epithelial mesenchymal transformation (EMT), the conversion of sessile epithelial cells into migratory fibroblast-like cells. EMT occurs during development, wound healing, and tumor progression. Growth factors, acting through mitogen-activated protein kinase (MAPK) cascades, regulate expression of Slug and Snail. Expression of Snail family transcription factors appears to be elevated in UVR-induced murine squamous cell carcinomas (SCC). We report here that ultraviolet radiation (UVR), which activates MAPK cascades, also stimulates Snail and Slug expression in epidermal keratinocytes. UVR exposure transiently elevated Slug and Snail mRNA expression in human keratinocytes in vitro and mouse epidermis in vivo. This induction was mediated, at least in part, through the ERK and p38 MAPK cascades, as pharmacological inhibition of these cascades partially or completely blocked Slug and Snail induction by UVR. On the other hand, UVR induction of Slug and Snail was enhanced by inhibition of JNK. Slug appears to play a functional role in the acute response of keratinocytes to UVR, as UVR induction of keratin 6 in the epidermis of Slug knockout mice was markedly delayed compared to wild-type mice. Slug and Snail are known to regulate molecules important in the cytoskeleton, intercellular adhesion, cell motility, and apoptosis, thus it seems probable that transiently or persistently elevated expression of these factors fosters the progression of UVR-induced SCC. © 2007 Wiley-Liss, Inc. [source] Proteomic profiling of tandem affinity purified 14-3-3 protein complexes in Arabidopsis thalianaPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 11 2009Ing-Feng Chang Abstract In eukaryotes, 14-3-3 dimers regulate hundreds of functionally diverse proteins (clients), typically in phosphorylation-dependent interactions. To uncover new clients, 14-3-3 omega (At1g78300) from Arabidopsis was engineered with a "tandem affinity purification" tag and expressed in transgenic plants. Purified complexes were analyzed by tandem MS. Results indicate that 14-3-3 omega can dimerize with at least 10 of the 12 14-3-3 isoforms expressed in Arabidopsis. The identification here of 121 putative clients provides support for in vivo 14-3-3 interactions with a diverse array of proteins, including those involved in: (i) Ion transport, such as a K+ channel (GORK), a Cl, channel (CLCg), Ca2+ channels belonging to the glutamate receptor family (1.2, 2.1, 2.9, 3.4, 3.7); (ii) hormone signaling, such as ACC synthase (isoforms ACS-6, -7 and -8 involved in ethylene synthesis) and the brassinolide receptors BRI1 and BAK1; (iii) transcription, such as 7 WRKY family transcription factors; (iv) metabolism, such as phosphoenol pyruvate carboxylase; and (v) lipid signaling, such as phospholipase D (, and ,). More than 80% (101) of these putative clients represent previously unidentified 14-3-3 interactors. These results raise the number of putative 14-3-3 clients identified in plants to over 300. [source] | |||||||||||||