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AP-1 melanocyte

Katelynn K Campbell, Jerad M Gardner, Kim Hall, Amanda Osborne, Sara C Shalin
BACKGROUND: Metastatic melanoma in sentinel lymph nodes is often elusive to detect with morphology alone. Per American Joint Committee on Cancer staging guidelines, a single atypical melanocyte in lymph node qualifies as metastasis, whether identified by morphology or immunohistochemistry, but single cell staining must be convincing. We propose that the use of a second immunohistochemical run performed on a single slide will allow for more confident diagnosis of micrometastases. MATERIALS AND METHODS: We designed a technical study to determine whether a second antibody application on previously stained slides can successfully detect the same population of cells...
November 28, 2018: Applied Immunohistochemistry & Molecular Morphology: AIMM
Hong Cai, Eun-Ae Cho, Yue Li, Jim Sockler, Christopher R Parish, Beng H Chong, Jarem Edwards, Tristan J Dodds, Peter M Ferguson, James S Wilmott, Richard A Scolyer, Gary M Halliday, Levon M Khachigian
Melanoma incidence is increasing worldwide, and although drugs such as BRAF/MEK small-molecule inhibitors and immune checkpoint antibodies improve patient outcomes, most patients ultimately fail these therapies and alternative treatment strategies are urgently needed. DNAzymes have recently undergone clinical trials with signs of efficacy and no serious adverse events attributable to the DNAzyme. Here we investigated c-Jun expression in human primary and metastatic melanoma. We also explored the role of T cell immunity in DNAzyme inhibition of primary melanoma growth and the prevention of growth in non-treated tumors after the cessation of treatment in a mouse model...
September 2018: Oncogene
Cécile Campagne, Léa Ripoll, Floriane Gilles-Marsens, Graça Raposo, Cédric Delevoye
Melanocytes are specialized cells that generate unique organelles called melanosomes in which melanin is synthesized and stored. Melanosome biogenesis and melanocyte pigmentation require the transport and delivery of melanin synthesizing enzymes, such as tyrosinase and related proteins (e.g., TYRP1), from endosomes to maturing melanosomes. Among the proteins controlling endosome-melanosome transport, AP-1 together with KIF13A coordinates the endosomal sorting and trafficking of TYRP1 to melanosomes. We identify here β1-adaptin AP-1 subunit-derived peptides of 5 amino acids that block the interaction of KIF13A with AP-1 in cells...
February 14, 2018: International Journal of Molecular Sciences
K Maurus, A Hufnagel, F Geiger, S Graf, C Berking, A Heinemann, A Paschen, S Kneitz, C Stigloher, E Geissinger, C Otto, A Bosserhoff, M Schartl, S Meierjohann
The MAPK pathway is activated in the majority of melanomas and is the target of therapeutic approaches. Under normal conditions, it initiates the so-called immediate early response, which encompasses the transient transcription of several genes belonging to the AP-1 transcription factor family. Under pathological conditions, such as continuous MAPK pathway overactivation due to oncogenic alterations occurring in melanoma, these genes are constitutively expressed. The consequences of a permanent expression of these genes are largely unknown...
September 7, 2017: Oncogene
Patrick Schummer, Silke Kuphal, Lily Vardimon, Anja K Bosserhoff, Melanie Kappelmann
A fundamental event in the development and progression of malignant melanoma is the de-regulation of cancer-relevant transcription factors. We recently showed that c-Jun is a main regulator of melanoma progression and, thus, is the most important member of the AP-1 transcription factor family in this disease. Surprisingly, no cancer-related specific c-Jun target genes in melanoma were described in the literature, so far. Therefore, we focused on pre-existing ChIP-Seq data (Encyclopedia of DNA Elements) of 3 different non-melanoma cell lines to screen direct c-Jun target genes...
May 3, 2016: Cancer Biology & Therapy
Sarmistha Mahanty, Keerthana Ravichandran, Praneeth Chitirala, Jyothi Prabha, Riddhi Atul Jani, Subba Rao Gangi Setty
Melanosomes are a type of lysosome-related organelle that is commonly defective in Hermansky-Pudlak syndrome. Biogenesis of melanosomes is regulated by BLOC-1, -2, -3, or AP-1, -3 complexes, which mediate cargo transport from recycling endosomes to melanosomes. Although several Rab GTPases have been shown to regulate these trafficking steps, the precise role of Rab9A remains unknown. Here, we found that a cohort of Rab9A associates with the melanosomes and its knockdown in melanocytes results in hypopigmented melanosomes due to mistargeting of melanosomal proteins to lysosomes...
January 2016: Pigment Cell & Melanoma Research
Y Bermudez
No abstract text is available yet for this article.
December 2014: British Journal of Dermatology
P Wäster, I Rosdahl, K Öllinger
BACKGROUND: Ultraviolet (UV) radiation constitutes an important risk factor for malignant melanoma, but the wavelength responsible for the initiation of this disease is not fully elucidated. Solar UV induces multiple signalling pathways that are critical for initiation of apoptotic cell death as a cellular defence against malignant transformation. OBJECTIVES: To evaluate the involvement of the transcription factors nuclear factor (NF)-κB and activator protein (AP)-1 in the signalling pathways induced by UVA or UVB irradiation in human melanocytes...
December 2014: British Journal of Dermatology
Jie Fang, Deping Han, Jinsheng Hong, Hengshan Zhang, Ying Ying, Yeping Tian, Lurong Zhang, Jianhua Lin
Alpha-melanocyte stimulating hormone (α-MSH) plays a crucial role in the regulation of immune and inflammatory reactions. Here we report that SVα-MSH, a novel α-MSH analog, could ameliorate the clinical severity of experimental autoimmune encephalomyelitis (EAE) in a preventive and therapeutic manner. SVα-MSH treatment induced the production of regulatory T (Treg) cells and reduced the Th17 cells in the CNS of EAE mice. SVα-MSH-treated PLP peptide 139-151-specific T cells showed a down-regulation of T cell activation markers CD69 and CD134...
April 15, 2014: Journal of Neuroimmunology
Geeta Lal, Piedad Gomez Contreras, Mikhail Kulak, George Woodfield, Thomas Bair, Frederick E Domann, Ronald J Weigel
Extracellular matrix 1 (ECM1) is over-expressed in multiple epithelial malignancies. However, knowledge regarding the expression of ECM1 in melanomas and the mechanisms of ECM1 regulation is limited. In this study, we found that ECM1 is over-expressed in several melanoma cell lines, when compared to primary melanocytes, and furthermore, that ECM1 expression paralleled that of TFAP2C levels in multiple cell lines. Knockdown of TFAP2C in the A375 cell line with siRNA led to a reduction in ECM1 expression, and upregulation of TFAP2C with adenoviral vectors in the WM793 cell line resulted in ECM1 upregulation...
2013: PloS One
Jarred J Bultema, Santiago M Di Pietro
Lysosome-related organelles (LROs) exist in specialized cells to serve specific functions and typically co-exist with conventional lysosomes. The biogenesis of LROs is known to utilize much of the common protein machinery used in the transport of integral membrane proteins to lysosomes. Consequently, an outstanding question in the field has been how specific cargoes are trafficked to LROs instead of lysosomes, particularly in cells that simultaneously produce both organelles. One LRO, the melanosome, is responsible for the production of the pigment melanin and has long been used as a model system to study the formation of specialized LROs...
January 2013: Small GTPases
Min-Ho Jeong, Kwang-Mo Yang, Jung-Ki Kim, Byung-Hyouk Nam, Gi-Yong Kim, Sang-Wha Lee, Su-Yeong Seo, Wol-Soon Jo
The control of melanogenesis is an important strategy in the treatment of abnormal skin pigmentation for cosmetic purposes. The aim of the present study was to investigate the anti-melanogenic effect of Asterina pectinifera (A. pectinifera) extracts by cell-free mushroom tyrosinase assay, cellular tyrosinase assay, melanin content assay and the analysis of related protein expression in melan-a cells. A. pectinifera was extracted with 80% methanol (80-MAP) and further fractionated with hexane (He-AP) and ethyl acetate (EA-AP)...
January 2013: International Journal of Molecular Medicine
Ahmad Jalili, Christine Wagner, Mikhail Pashenkov, Gaurav Pathria, Kirsten D Mertz, Hans R Widlund, Mathieu Lupien, Jean-Philippe Brunet, Todd R Golub, Georg Stingl, David E Fisher, Sridhar Ramaswamy, Stephan N Wagner
Resistance to BRAF(V600E) inhibitors is associated with reactivation of mitogen-activated protein kinase (MAPK) signaling at different levels in melanoma. To identify downstream effectors of MAPK signaling that could be used as potential additional therapeutic targets for BRAF(V600E) inhibitors, we used hTERT/CDK4R24C/p53DD-immortalized primary human melanocytes genetically modified to ectopically express BRAF ( V600E ) or NRAS ( G12D ) and observed induction of the AP-1 transcription factor family member c-Jun...
November 7, 2012: Journal of the National Cancer Institute
Mamoru Ishii, Athena C Arias, Liqiong Liu, Yi-Bu Chen, Marianne E Bronner, Robert E Maxson
Cranial neural crest cells give rise to ectomesenchymal derivatives such as cranial bones, cartilage, smooth muscle, dentin, as well as melanocytes, corneal endothelial cells, and neurons and glial cells of the peripheral nervous system. Previous studies have suggested that although multipotent stem-like cells may exist during the course of cranial neural crest development, they are transient, undergoing lineage restriction early in embryonic development. We have developed culture conditions that allow cranial neural crest cells to be grown as multipotent stem-like cells...
November 20, 2012: Stem Cells and Development
M Kappelmann, S Kuphal, G Meister, L Vardimon, A-K Bosserhoff
A fundamental event in the development and progression of malignant melanoma is the deregulation of cancer-relevant transcription factors. We recently showed that c-Jun is a main regulator of tumor progression in melanoma and thus the most important member of the AP-1 transcription factor family for this disease. Interestingly, we revealed that c-Jun expression was regulated on the post-transcriptional level and therefore speculated that miRNAs could be involved in c-Jun regulation. We determined seed sequences for miR-125b and miR-527 in the coding region of c-Jun mRNA that hints at the direct involvement of miRNA-dependent regulation on the protein level...
June 13, 2013: Oncogene
Anand Sitaram, Megan K Dennis, Rittik Chaudhuri, Wilfredo De Jesus-Rojas, Danièle Tenza, Subba Rao Gangi Setty, Christopher S Wood, Elena V Sviderskaya, Dorothy C Bennett, Graça Raposo, Juan S Bonifacino, Michael S Marks
Cell types that generate unique lysosome-related organelles (LROs), such as melanosomes in melanocytes, populate nascent LROs with cargoes that are diverted from endosomes. Cargo sorting toward melanosomes correlates with binding via cytoplasmically exposed sorting signals to either heterotetrameric adaptor AP-1 or AP-3. Some cargoes bind both adaptors, but the relative contribution of each adaptor to cargo recognition and their functional interactions with other effectors during transport to melanosomes are not clear...
August 2012: Molecular Biology of the Cell
Jarred J Bultema, Andrea L Ambrosio, Carolyn L Burek, Santiago M Di Pietro
Lysosome-related organelles (LROs) are synthesized in specialized cell types where they largely coexist with conventional lysosomes. Most of the known cellular transport machinery involved in biogenesis are ubiquitously expressed and shared between lysosomes and LROs. Examples of common components are the adaptor protein complex-3 (AP-3) and biogenesis of lysosome-related organelle complex (BLOC)-2. These protein complexes control sorting and transport of newly synthesized integral membrane proteins from early endosomes to both lysosomes and LROs such as the melanosome...
June 1, 2012: Journal of Biological Chemistry
Rancés Blanco, Enrique Rengifo, Charles E Rengifo, Mercedes Cedeño, Milagros Frómeta, Adriana Carr
The evaluation of 14F7 Mab (anti-N-glycolyl GM3 ganglioside) immunorecognition in normal skin, cutaneous malignant melanoma (CMM), and in lymph node metastases (LNM) has been previously reported. In this work we extended the study to benign (BMN) and dysplastic (DMN) melanocytic nevi, basal (BCC), and squamous cell carcinoma (SCC). Immunohistochemical assays with 14F7 followed by a biotinylated link universal and streptavidin-AP in normal and pathological tissues were made. No reaction of 14F7 in normal skin (0/10) as well as a low reactivity in BMN (2/11) and DMN (1/7) was detected...
2011: ISRN Dermatology
César López-Camarillo, Elena Aréchaga Ocampo, Mavil López Casamichana, Carlos Pérez-Plasencia, Elizbeth Alvarez-Sánchez, Laurence A Marchat
Solar ultraviolet (UV) radiation is an important environmental factor that leads to immune suppression, inflammation, photoaging, and skin carcinogenesis. Here, we reviewed the specific signal transduction pathways and transcription factors involved in the cellular response to UV-irradiation. Increasing experimental data supporting a role for p38, MAPK, JNK, ERK1/2, and ATM kinases in the response network to UV exposure is discussed. We also reviewed the participation of NF-κB, AP-1, and NRF2 transcription factors in the control of gene expression after UV-irradiation...
2012: International Journal of Molecular Sciences
Michele Carbone, Haining Yang
Malignant mesothelioma is an aggressive malignancy related to asbestos and erionite exposure. AP-1 transcriptional activity and the NF-κB signaling pathway have been linked to mesothelial cell transformation and tumor progression. HGF and c-Met are highly expressed in mesotheliomas. Phosphoinositide 3-kinase, AKT, and the downstream mTOR are involved in cell growth and survival, and they are often found to be activated in mesothelioma. p16(INK4a) and p14(ARF) are frequently inactivated in human mesothelioma, and ∼50% of mesotheliomas contain the NF2 mutation...
February 1, 2012: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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