5,958 research outputs found
Melanosome-autonomous regulation of size and number: the OA1 receptor sustains PMEL expression.
No full textTbx3 represses E-cadherin expression and enhances melanoma invasiveness.
No full textThe T-box transcription factors Tbx2 and Tbx3 are overexpressed in many cancers and in melanoma promote proliferation by actively suppressing senescence. Whether they also contribute to tumor progression via other mechanisms is not known. Here, we identify a novel role for these factors, providing evidence that Tbx3, and potentially Tbx2, directly repress the expression of E-cadherin, a keratinocyte-melanoma adhesion molecule whose loss is required for the acquisition of an invasive phenotype. Overexpression of Tbx2 and Tbx3 in melanoma cells down-regulates endogenous E-cadherin expression, whereas depletion of Tbx3, but not Tbx2, increases E-cadherin mRNA and protein levels and decreases melanoma invasiveness in vitro. Consistent with these observations, in melanoma tissue, Tbx3 and E-cadherin expression are inversely correlated. Depletion of Tbx3 also leads to substantial up-regulation of Tbx2. The results suggest that Tbx2 and Tbx3 may play a dual role during the radial to vertical growth phase transition by both inhibiting senescence via repression of p21(CIP1) expression, and enhancing melanoma invasiveness by decreasing E-cadherin levels
Melanosome-autonomous regulation of size and number: the OA1 receptor sustains PMEL expression.
No full textLittle is known as to how cells ensure that organelle size and number are coordinated to correctly couple organelle biogenesis to the demands of proliferation or differentiation. OA1 is a melanosome-associated G-protein-coupled receptor involved in melanosome biogenesis during melanocyte differentiation. Cells lacking OA1 contain fewer, but larger, mature melanosomes. Here, we show that OA1 loss of function reduces both the basal expression and the α-melanocyte-stimulating hormone/cAMP-dependent induction of the microphthalmia-associated transcription factor (MITF), the master regulator of melanocyte differentiation. In turn, this leads to a significant reduction in expression of PMEL, a major melanosomal structural protein, but does not affect tyrosinase and melanin levels. In line with its pivotal role in sensing melanosome maturation, OA1 expression rescues melanosome biogenesis, activates MITF expression and thereby coordinates melanosome size and number, providing a quality control mechanism for the organelle in which resides. Thus, resident sensor receptors can activate a transcriptional cascade to specifically promote organelle biogenesis
Cr(VI) and Cr(III)-Based Conversion Coatings on Zinc
No full textWith the aims of understanding the protective mechanism of chromate conversion coatings and developing alternatives to chromate treatments, the physical natures and corrosion properties of Cr(VI) and Cr(III) treated zinc have been investigated in this work. The Cr(VI) treatments were carried out in dichromate and sulfuric acid solution with different dipping times. The Cr(III) treatments were carried out in two commercial solutions (A and B). The thickness of the coatings was measured using ellipsometry. The morphologies and the compositions of the treated zinc have been studied by means of SEM, AFM, AES, FTIR and XPS. The drying temperature influence on the corrosion performance of the Cr(VI)âtreated zinc has been investigated. The Volta potential in treated and untreated areas has been measured using scanning Kelvin probe (SKP) and SKPFM. The corrosion behavior of the Cr(VI) and Cr(III) treated zinc has been investigated using polarization, electrochemical impedance measurements (EIS), and salt spray tests. Both Cr(VI) and Cr(III) species were detected by XPS in the outermost layer of the Cr(VI) coatings, while no Cr(VI) species was found in the Cr(III) coatings. AES depth profile results show that chromium oxides are the main components in the Cr(VI) coatings. Zinc oxide is mainly located at the chromium oxides / zinc interface. The Cr(III) coating is a mixture of chromium oxides and zinc oxide. Both the Cr(VI) and the Cr(III) treatments can supply corrosion protection to zinc. The corrosion resistance of the Cr(III)-B coating is greater than that of the Cr(III)-A coating. However, the inhibition of the corrosion of zinc by Cr(VI) coating is more effective than by the Cr(III) coatings. The inhibition of the corrosion of zinc by the Cr(VI) and the Cr(III) treatments is discussed, and future research topics are suggested.Mechanical, Maritime and Materials Engineerin
The retinoblastoma protein modulates Tbx2 functional specificity
No full textTbx2 is a member of a large family of transcription factors defined by homology to the T-box DNA-binding domain. Tbx2 plays a key role in embryonic development, and in cancer through its capacity to suppress senescence and promote invasiveness. Despite its importance, little is known of how Tbx2 is regulated or how it achieves target gene specificity. Here we show that Tbx2 specifically associates with active hypophosphorylated retinoblastoma protein (Rb1), a known regulator of many transcription factors involved in cell cycle progression and cellular differentiation, but not with the Rb1-related proteins p107 or p130. The interaction with Rb1 maps to a domain immediately carboxy-terminal to the T-box and enhances Tbx2 DNA binding and transcriptional repression. Microarray analysis of melanoma cells expressing inducible dominant-negative Tbx2, comprising the T-box and either an intact or mutated Rb1 interaction domain, shows that Tbx2 regulates the expression of many genes involved in cell cycle control and that a mutation which disrupts the Rb1-Tbx2 interaction also affects Tbx2 target gene selectivity. Taken together, the data show that Rb1 is an important determinant of Tbx2 functional specificity
Transcription and cancer.
No full textThe normal growth, development and function of an organism requires precise and co-ordinated control of gene expression. A major part of this control is exerted by regulating messenger RNA (mRNA) production and involves complex interactions between an array of transcriptionally active proteins and specific regulatory DNA sequences. The combination of such proteins and DNA sequences is specific for given gene or group of genes in a particular cell type and the proteins regulating the same gene may vary between cell types. In addition the expression or activity of these regulatory proteins may be modified depending on the state of differentiation of a cell or in response to an external stimulus. Thus, the differentiation of embryonic cells into diverse tissues is achieved and the mature structure and function of the organism is maintained. This review focusses on the role of perturbations of these transcriptional controls in neoplasia. Deregulation of transcription may result in the failure to express genes responsible for cellular differentiation, or alternatively, in the transcription of genes involved in cell division, through the inappropriate expression or activation of positively acting transcription factors and nuclear oncogenes. Whether the biochemical abnormalities that lead to the disordered growth and differentiation of a malignant tumour affect cell surface receptors, membrane or cytoplasmic signalling proteins or nuclear transcription factors, the end result is the inappropriate expression of some genes and failure to express others. Current research is starting to elucidate which of the elements of this complicated system are important in neoplasia
SL4/PASPCR Aaron Lerner Lecture Signalling and transcription in melanoma stem-like cells
No full textMitf from neural crest to melanoma: signal transduction and transcription in the melanocyte lineage.
No full textMelanocyte development and malignant melanoma.
No full textMalignant melanoma is a notoriously aggressive disease that can affect relatively young individuals and whose incidence is rising at an alarming rate. Unlike many cancers, metastatic melanoma is poorly responsive to current therapies and mutations affecting p53, the retinoblastoma gene product or Ras which occur frequently in many other cancer types, appear to be rare or at least relatively late events in the progression of the disease. Recent advances in our understanding of the disease at the molecular level have indicated that in addition to the loss of cell cycle checkpoints which may be common to all cancers, malignant melanoma shares many characteristics in common with developmental precursors to melanocytes, the mature pigment producing cells of the skin and hair follicles which are responsible for skin and hair colour. This review therefore focuses on the signalling pathways that play a crucial role in the development of the melanocyte lineage which are subject to deregulation in malignant melanoma namely signalling by receptor tyrosine kinases, the Wnt signalling pathway, as well as loss of the p16INK4a cyclin-dependent kinase inhibitor. Intriguingly all three pathways impact on the expression or function of the microphthalmia-associated transcription factor which plays an essential role in melanocyte development
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