3,144 research outputs found
MC1R functions, expression and implications for targeted therapy
Get PDFThe G protein-coupled MC1R is expressed in melanocytes and has a pivotal role in human skin pigmentation, with reduced function in human genetic variants exhibiting a red hair phenotype and increased melanoma predisposition. Beyond its role in pigmentation, MC1R is increasingly recognized as promoting UV-induced DNA damage repair. Consequently, there is mounting interest in targeting MC1R for therapeutic benefit. However, whether MC1R expression is restricted to melanocytes or is more widely expressed remains a matter of debate. In this paper, we review MC1R function and highlight that unbiased analysis suggests that its expression is restricted to melanocytes, granulocytes, and the brain
Colin Humphris
No full text"Colin Humphris 2 Sqdrn. RAAF. 1941 - 1942 Author of - 'Trapped on Timor' (as a result of bombing of Darwin Feb. 19, 1942)".Colin Humphris. 2 Squadron, Royal Australian Air Force 1941 - 1942. Author of - 'Trapped on Timor' (as a result of bombing of Darwin February 19, 1942)
Interview with Colin Wilson, part 4, undated
No full textInterview with Colin Wilson, part 4, features an interview with author Colin Wilson in which he discusses his views regarding society and art, his reclusive nature, and the intellectual and fantastical elements of his works, undated
Interview with Colin Wilson, part 2, undated
No full textInterview with Colin Wilson, part 2, features an interview with author Colin Wilson in which he discusses his views regarding society and art, his reclusive nature, and the intellectual and fantastical elements of his works, undated
Providence College Faculty Author Series 2017-2018: D. Colin Jaundrill
No full textIn this installment of the Faculty Authors Series, D. Colin Jaundrill (History, Providence College) discusses his newest book, Samurai to Soldier: Remaking Military Service in Nineteenth-Century Japan
Providence College Faculty Author Series 2017-2018: D. Colin Jaundrill
Get PDFIn this installment of the Faculty Authors Series, D. Colin Jaundrill (History, Providence College) discusses his newest book, Samurai to Soldier: Remaking Military Service in Nineteenth-Century Japan
Interview with Colin Jerolmack
No full textColin Jerolmack is an Assistant Professor at New York University
in Sociology and Environmental Studies. He is the author of The
Global Pigeon (forthcoming) and an alumnus of the Robert Wood
Johnson Foundation Scholars in Health Policy Program at Harvard
University
Colin Fraser
No full textPhotograph - Colin Fraser (third from right) in a loaded scow leaving for Fort Chipewyan from Athabasca, Alberta. A group of men are also standing on the pie
The MITF regulatory network in melanoma
Get PDFBidirectional interactions between plastic tumor cells and the microenvironment critically impact tumor evolution and metastatic dissemination by enabling cancer cells to adapt to microenvironmental stresses by switching phenotype. In melanoma, a key determinant of phenotypic identity is the microphthalmia-associated transcription factor MITF that promotes proliferation, suppresses senescence, and anticorrelates with immune infiltration and therapy resistance. What determines whether MITF can activate or repress genes associated with specific phenotypes, or how signaling regulating MITF might impact immune infiltration is poorly understood. Here, we find that MITF binding to genes associated with high MITF is via classical E/M-box motifs, but genes downregulated when MITF is high contain FOS/JUN/AP1/ATF3 sites. Significantly, the repertoire of MITF-interacting factors identified here includes JUN and ATF3 as well as many previously unidentified interactors. As high AP1 activity is a hallmark of MITFLow, invasive, slow-cycling, therapy resistant cells, the ability of MITF to repress AP1-regulated genes provides an insight into how MITF establishes and maintains a pro-proliferative phenotype. Moreover, although β-catenin has been linked to immune exclusion, many Hallmark β-catenin signaling genes are associated with immune infiltration. Instead, low MITF together with Notch signaling is linked to immune infiltration in both mouse and human melanoma tumors
Role and regulation of MITF in melanocytes and melanoma
Get PDFOne key to understanding how cells integrate and how they respond to diverse stimuli in order to direct a transcriptional response is knowing how a transcription factor may be directed to an appropriate subset of its target genes. One mechanism with which this may be achieved is by modulation of the transcription factor’s post-translational modification status. The microphthalmia-associated transcription factor (MITF) is the master regulator of the melanocyte lineage, and it is also a lineage addiction gene in melanoma. Low or high levels of MITF expression induce a reversible cell cycle arrest. Invasive behaviour is characteristic of low MITF expression; differentiation a product of high MITF activity; and moderate levels of MITF expression promote proliferation. A major, unaddressed problem is how DNA binding by MITF may be differentially directed such that it regulates either a proliferation-associated or a differentiation-associated gene expression programme appropriate to the cellular microenvironment. This thesis explores the function and regulation of the signalling pathways controlling novel post-translational modifications of MITF. One such modification, in the DNA binding domain of MITF, defines a key switch that controls MITF’s DNA binding affinity and specificity. Moreover, a novel set of MITF target genes are revealed that extend its control beyond pigmentation and cell cycle regulation to implicate MITF as an overall regulator of cell behaviour in the melanocyte lineage
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