Arsenic-induced suppression of kidney cell proliferation and the transcriptional coregulator MAML1.
Mastermind-like 1 (MAML1) is a transcriptional coregulator of diverse/multiple activators, such as Notch, p53, myocyte enhancer factor 2C, NF-κB, beta-catenin, papillomavirus E6 proteins, early growth response 1 and runt-related transcription factor 2. Thus, MAML1 functions in various signaling pathways, most of them connected to cell proliferation, which suggests that MAML1 might play a potential role as a cell proliferation marker. In this study we show that MAML1 expression in the kidney correlates in silico with established cell proliferation markers including PCNA, CDC2 and XRCC5 (Ku80). Over-expression of MAML1 increased proliferation of human embryonic kidney (HEK) 293 cells, while MAML1 downregulation by siRNA decreased cell proliferation. Exposure of HEK293 cells to inorganic arsenic (arsenite) showed reduced levels of MAML1, in combination with a decreased proliferation rate. Our findings provide evidence that arsenic can inhibit proliferation of embryonic kidney cells, possibly through reduction of MAML1 gene expression.
Institute of Environmental Medicine, Karolinska Institutet, S-171 77 Stockholm, Sweden. Annika.Wallberg@ki.se.
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Pournara
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T
Holmlund
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Y
Lu
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Ceder
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Putnik
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Grafström
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Vahter
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Wallberg
D001151:Arsenic / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects*; D057809:HEK293 Cells; D006801:Humans; D007668:Kidney / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
D004268:DNA-Binding Proteins; C430872:MAML1 protein, human; D034741:RNA, Small Interfering; D014157:Transcription Factors; D001151:Arsenic