About: A short acidic motif in ARF guards against mitochondrial dysfunction and melanoma susceptibility

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About: A short acidic motif in ARF guards against mitochondrial dysfunction and melanoma susceptibility Goto Sponge NotDistinct Permalink

An Entity of Type : http://linked.opendata.cz/ontology/domain/vavai/Vysledek, within Data Space : linked.opendata.cz associated with source document(s)

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rdf:type	skos:Concept http://linked.opendata.cz/ontology/domain/vavai/Vysledek
Description	ARF is a small, highly basic protein that can be induced by oncogenic stimuli and exerts growth-inhibitory and tumour-suppressive activities through the activation of p53. Here we show that, in human melanocytes, ARF is cytoplasmic, constitutively expressed, and required for maintaining low steady-state levels of superoxide under conditions of mitochondrial dysfunction. This mitochondrial activity of ARF is independent of its known autophagic and p53-dependent functions, and involves the evolutionarily conserved acidic motif GHDDGQ, which exhibits weak homology to BCL-2 homology 3 (BH3) domains and mediates interaction with BCL-xL-an important regulator of mitochondrial redox homeostasis. Melanoma-predisposing CDKN2A germline mutations, which affect conserved glycine and aspartate residues within the GHDDGQ motif, impair the ability of ARF to control superoxide production and suppress growth of melanoma cells in vivo. These results reveal an important cell-protective function of ARF that links mitochondrial dysfunction and susceptibility to melanoma. ARF is a small, highly basic protein that can be induced by oncogenic stimuli and exerts growth-inhibitory and tumour-suppressive activities through the activation of p53. Here we show that, in human melanocytes, ARF is cytoplasmic, constitutively expressed, and required for maintaining low steady-state levels of superoxide under conditions of mitochondrial dysfunction. This mitochondrial activity of ARF is independent of its known autophagic and p53-dependent functions, and involves the evolutionarily conserved acidic motif GHDDGQ, which exhibits weak homology to BCL-2 homology 3 (BH3) domains and mediates interaction with BCL-xL-an important regulator of mitochondrial redox homeostasis. Melanoma-predisposing CDKN2A germline mutations, which affect conserved glycine and aspartate residues within the GHDDGQ motif, impair the ability of ARF to control superoxide production and suppress growth of melanoma cells in vivo. These results reveal an important cell-protective function of ARF that links mitochondrial dysfunction and susceptibility to melanoma. (en)
Title	A short acidic motif in ARF guards against mitochondrial dysfunction and melanoma susceptibility A short acidic motif in ARF guards against mitochondrial dysfunction and melanoma susceptibility (en)
skos:prefLabel	A short acidic motif in ARF guards against mitochondrial dysfunction and melanoma susceptibility A short acidic motif in ARF guards against mitochondrial dysfunction and melanoma susceptibility (en)
skos:notation	RIV/61989592:15110/14:33150873!RIV15-MSM-15110___
http://linked.open...avai/riv/aktivita	P Z
http://linked.open...avai/riv/aktivity	P(ED0030/01/01), Z(MSM6198959216)
http://linked.open...iv/cisloPeriodika	5348
http://linked.open...vai/riv/dodaniDat	2015
http://linked.open...aciTvurceVysledku	Bártek, Jiří Mistrík, Martin
http://linked.open.../riv/druhVysledku	J - Článek v odborném periodiku
http://linked.open...iv/duvernostUdaju	S - Úplné a pravdivé údaje nepodléhající ochraně podle zvláštních právních předpisů
http://linked.open...titaPredkladatele	Univerzita Palackého v Olomouci / Lékařská fakulta
http://linked.open...dnocenehoVysledku	1163
http://linked.open...ai/riv/idVysledku	RIV/61989592:15110/14:33150873
http://linked.open...riv/jazykVysledku	eng - angličtina
http://linked.open.../riv/klicovaSlova	DNA-DAMAGE; HUMAN FIBROBLASTS; GERMLINE MUTATION; SOMATIC MUTATIONS; MALIGNANT-MELANOMA; HUMAN CANCER; NUCLEOLAR LOCALIZATION; OXIDATIVE-PHOSPHORYLATION; CELL-CYCLE ARREST; TUMOR-SUPPRESSOR PROTEIN (en)
http://linked.open.../riv/klicoveSlovo	NUCLEOLAR LOCALIZATION CELL-CYCLE ARREST GERMLINE MUTATION HUMAN FIBROBLASTS MALIGNANT-MELANOMA OXIDATIVE-PHOSPHORYLATION SOMATIC MUTATIONS TUMOR-SUPPRESSOR PROTEIN DNA-DAMAGE HUMAN CANCER
http://linked.open...odStatuVydavatele	GB - Spojené království Velké Británie a Severního Irska
http://linked.open...ontrolniKodProRIV	[F31B44C12E99]
http://linked.open...i/riv/nazevZdroje	Nature Communications
http://linked.open...in/vavai/riv/obor	EB
http://linked.open...ichTvurcuVysledku	2 (xsd:int)
http://linked.open...cetTvurcuVysledku	8 (xsd:int)
http://linked.open...vavai/riv/projekt	Biomedicine for regional development and human resources
http://linked.open...UplatneniVysledku	2014
http://linked.open...v/svazekPeriodika	5
http://linked.open...iv/tvurceVysledku	Bártek, Jiří Mistrík, Martin Bartkova, J. Christensen, C. Guldberg, P. Hall, A. Lange, Mk Ralfkiaer, U.
http://linked.open...ain/vavai/riv/wos	000345624200004
http://linked.open...n/vavai/riv/zamer	Modulation of signalling and regulatory pathways in normal and cancer cells
issn	2041-1723
number of pages	15 (xsd:int)
http://bibframe.org/vocab/doi	10.1038/ncomms6348
http://localhost/t...ganizacniJednotka	15110

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