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Microphthalmia-Associated Transcription Family Translocation Renal Cell Cancer
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
The transcription factor EB gene (TFEB) located on chromosome 6p21.1 spans 52 kb and encodes a 476 aa, 52 kDa protein (TFEB) with specificity for E-box sequences (5'-CANNTG-3') and involvement in PI3K-AKT-mTOR signaling pathway. Fusion between TFEB and translocation partner MALAT1 produces chromosome translocation t(6;11)(p21.1;q12) and t(6;11) RCC [36]. Also, in association with TFE3, TFEB activates the expression of CD40L in T cells, and thus participates in T-cell-dependent antibody responses in activated CD4(+) T cells and thymus-dependent humoral immunity. Further, TFEB recognizes and binds the CLEAR-box sequence (5'-GTCACGTGAC-3') present in the regulatory region of many lysosomal genes, thus activating the expression of lysosomal genes. TFEB also promotes expression of genes involved in autophagy, and specifically recognizes the gamma-E3 box present in the heavy-chain immunoglobulin enhancer. Finally, TFEB takes part in the signal transduction processes for normal vascularization of the placenta.
Vascular Smooth Muscle Cells
Published in John H. Barker, Gary L. Anderson, Michael D. Menger, Clinically Applied Microcirculation Research, 2019
Lars M. Rasmussen, Jens L. Andresen, Thomas Ledet
Although information about the characteristics of different vascular smooth muscle phenotypes have been gained using these techniques, almost nothing is known about the regulation of the differentiation processes. A major breakthrough in the understanding of skeletal muscle cell development could, however, be extrapolated to the regulation mechanisms of smooth muscle cell differentiation. The differentiation of skeletal muscle cells has been shown to be driven by the expression of members of a large family of basic helix-loop-helix transcription factors, now designated as the MyoD family.22,113 When expressed in mesenchymal cells, these proteins will bind to promotor regions in skeletal muscle cell specific genes, turning the transcription on, thereby making the cells into a skeletal muscle. Recently, sequence analysis of the smooth muscle cell specific gene, α-smooth muscle cell actin, revealed that the promotor of this gene contains a consensus region for the binding of proteins of the basic helix-loop-helix family, the so called “E-box”.86 Moreover, gel-shift analyses with smooth muscle cell nuclear extracts have indicated that proteins binding to this area are present in vascular smooth muscle cells. Transfection experiments have indicated that vascular smooth muscle cells contain endogenous, still unknown genes of this family that could be of importance in the differentiation of smooth muscle cells.86,116
Proto-Oncogene and Onco-Suppressor Gene Expression
Published in Enrique Pimentel, Handbook of Growth Factors, 2017
The nuclear phosphoprotein Max has an important role in the regulation of Myc activity. The max gene resides on human chromosome region 14q23. Max shares with Myc the presence of binding region, HLH, and leucine zipper motif in its sequence and is able to form specific dimers with Myc. The levels of Max RNA are relatively stable and Max protein expression is modestly induced after serum stimulation of resting mouse fibroblasts and are not altered during the process of cell differentiation.553 The inverse levels of Max and Myc protein expression in growth-arrested cells vs. proliferating cells suggest that Max may modulate Myc function in an antagonistic fashion.50 In quiescent cells, Max may exist predominantly in the form of a homodimer, whereas in growth factor-stimulated cells it forms a heterodimer with Myc. Phosphorylation of Max may also regulate its DNA-binding ability and its dimerization with Myc. Max-Myc heterodimers may activate gene transcription in a specific manner through the recognition of DNA elements (E boxes) containing the central CACGTG sequence. In quiescent cells there are little amounts of Myc protein and high amounts of Max protein, and Max would be bound to E boxes but not capable of activating transcription. The Max protein would thus act as a repressor of the expression of genes containing E box sequences in their promoter. In growth factor-stimulated cells, the concentration of Myc-Max heterodimers increases, which leads to activation of the transcriptional expression of genes containing E boxes.
Inhibition of ELF3 confers synthetic lethality of PARP inhibitor in non-small cell lung cancer
Published in Journal of Receptors and Signal Transduction, 2021
Yan Wang, Min Zuo, Hongtao Jin, Meina Lai, Jinfeng Luo, Zhiqiang Cheng
EMT could regulate transcription factor, zinc finger E-box binding homeobox 1, to mediate DNA damage response [25,26]. Moreover, EMT could modulate DNA damage response pathways to regulate PARP inhibitor resistance [27]. The role of ELF3 on DNA damage response was then determined. Immunofluorescence analysis showed that inhibition of ELF3 increased γH2AX foci accumulation while decreased RAD51 foci in PARP inhibitor-resistant NSCLC cells. Double-strand breaks generally triggers phosphorylation of H2AX to produce γH2AX [28], and γH2AX recruits other proteins to generate assembly of DNA repair proteins, thus playing an important role in DNA damage response [29]. RAD51 participates in DNA damage repair [30], and functions as biomarker of HR-mediated DNA damage repair [31]. LIM-domain only 2 could increase of γH2AX and decrease of RAD51 to inhibit HR-mediated DNA damage repair, sensitize tumor cells to PARP inhibitor [32]. Inhibition of bromodomain containing 4 induced HR deficiency via increase of γH2AX and decrease of RAD51, thus confering synthetic lethal with PARP inhibitors [33]. Therefore, inhibition of ELF3 reduced HR-mediated DNA damage repair ability in PARP inhibitor-resistant NSCLC cells. However, in addition to HR-mediated DNA damage repair, alternative NHEJ also participates in synthetic lethal therapies for PARP inhibitors [34]. The regulatory ability of ELF3 on NHEJ-mediated DNA damage repair in PARP inhibitor-resistant NSCLC cells should be further investigated.
24 hour patterning in gene expression of pineal neurosteroid biosynthesis in young chickens (Gallus gallus domesticus L.)
Published in Chronobiology International, 2021
Magdalena Chustecka, Natalia Blügental, Pawel Marek Majewski, Iwona Adamska
The avian central biological clock embraces the suprachiasmatic nuclei (SCN), the pineal gland, and the retina of the eye, as three equivalent independent clocks (Cassone 2014). It might be assumed that control of genes encoding the neurosteroidogenesis enzymes may be under two separate clocks: the SCN and the pineal gland. This may explain the lack of rhythm in constant darkness for Cyp11a1, Cyp7b1, and Srd5a3 genes. To conclude, our findings support the hypothesis that Cyp11a1, Cyp7b1, and Srd5a3 as candidate CCGs, since they were demonstrated as susceptible to clock control. To confirm this, promoters for these genes should be examined for the presence of the functional E-box sequence, through gene promoter analysis.
Curcumin reverses hepatic epithelial mesenchymal transition induced by trichloroethylene by inhibiting IL-6R/STAT3
Published in Toxicology Mechanisms and Methods, 2021
Weiya Cao, Yinci Zhang, Amin Li, Pan Yu, Li Song, Jiaojiao Liang, Niandie Cao, Jiafeng Gao, Ruyue Xu, Yongfang Ma, Xiaolong Tang
Snail is considered to be a key factor in regulating the EMT of tumor cells (Liu et al. 2020). It directly interacts with the E-box site in the E-cadherin promoter and inhibits its transcription. Our data suggest that TCE increases snail levels at both transcriptional and post-transcriptional levels. After 8 h of TCE treatment, both mRNA and protein were up-regulated, which proved this point. Other factors such as twist, ZEB, e2.2, and FOXC2 can also regulate the EMT process by indirectly inhibiting the transcription of E-cadherin (Sommariva and Gagliano 2020). Whether these factors are also involved in the EMT of HCC cells induced by TCE needs further study.