The carcinogenicity of nickel compounds has been confirmed and corroborated by numerous epidemiological studies in humans and carcinogenesis bioassays in animals . Although the mechanisms of nickel-induced carcinogenesis are not well-known, they are believed to involve genetic and epigenetic routes. Nickel compounds influence carcinogenesis by interfering with a variety of cellular targets. We found that nickel is a potent inhibitor in vivo of histone H4 acetylation, in both yeast and mammalian cells . It has preference to specific lysine residues in the N-terminal -S1GRGK5GGK8GLGK12GGAK16RH18RKVL22 histone H4, in which the sites of acetylation are clustered. The metal ion is able to bind histidine H18 in the N-terminal which protrude out from the nucleosome . We also found that an excellent tumour marker recently discovered and specifically induced by nickel, Cap43 protein, has a new mono-histidinic motif consisting of ten amino acids TRSRSHTSEG repeated three times in the C-terminus which is able to bind several metal ions in a cooperative way [4,5].
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|Titolo:||Molecular Mechanisms of Nickel Carcinogenesis: Nickel Binding to Histone H4 and Cap43 Protein|
|Data di pubblicazione:||2005|
|Appare nelle tipologie:||4.2 Abstract in Atti di convegno|